长春冰雪旅游节暨净月潭瓦萨国际滑雪节正式开幕【组图】

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- ?????? ??????? - ????? ???? ?????? ?????? ????? ???? ??? ???????? ???? ??????. ???? ???????? ?? ????? ?????? ?? ???????? ?? ???????? ??????, ?????. ????? ?? ?????? ?????? ????? ???? ?????. ????? ?????? ????? ??? ???? ????? ???????? ?????? ???????? ?? ????? ???? ??? ??????. ??????? ????? ???? ???????? ???? ?? ??????????? (????? ????????) ?? ??????, ?? ??????? ?? ???????? ???? ????? ????. ???? ?????? ?? ??????, ?? ?? ?????? ???? ???????, ??????? ????? ????? ????????.
- ?????? ?? ???????? - ??????? ????? ???? ????????, ?? ????? ???? ???????? ?? ??????. ??? ????? ?? ?????? ???? ?????, ?? ??? ?????? ?? ????? ??? ?????? ???? ?? ???? ????? ?? ?????? ?? ??????? ???? ????? ?? ???????? ?? ?? ????? ????.
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[????? ??? ???? | ?????]????? ???? ???? ?????? ???? ??????? ?? ??????? ????? ?????? ??????? ?????-???????, ??????? ?? ??????? ???????? ?? ??????. ????? ???????-???? ??????? ????, ????? (E) ???? ???????? ??? (S) ?????? ????? ?????-??????? (ES). ?????? ??????, ????? ?? ???? ?????? ????? P ?????? ?????. ????? (I) ???? ?????? ?? ?-E ?? ?-ES ?? ????? ?????????? Ki ?? Ki' ??????.

- ?????? ???????? ?????? ?????? ?-E, ?? ?? ?-ES. ????? ?????? ????? ?? ?-Km (????? ????? ????? ???????? ????????), ???? ???? ????? ?? ?-Vmax (????? ?? ????? ?????? ?????? ES ???? ????? ???? ?????? ?-ES).
- ??????? ?? ???????? ????? ??? ?-E ??-ES ?(Ki = Ki'). ?????? ??? ????? ?? ?-Km (????? ??????? ?? ?-Km ?????? ????? ?????? ?????), ?????? ??????? ?? ?-Vmax (????? ??????? ????? ?????? ?????? ?????).
- ?????? ??????? ?????? ?? ?-E ??? ?-ES, ?? ?????? ???? ?????? ?? ?????? ???? (Ki ≠ Ki'). ?????, ?????? ??? ??????? ?? ???????? ???????? (??????? ?-Km) ??? ?????? ?????? ?????? ES (??????? Vmax).
???? ?? ?????? ???? ?????????, ?????? ?????? ????? ????? ????? ?? ??????? ????? ???????? ?????. ????? ?? ????? ??? ????? ????? ???? ??? ???? ????? ????? ?????, ??? ??? ???????. ??, ????, ???? ???? ??????? ?? ??????? ?' ?? ??? ?????? ???, ?? ????? ???? ?? ?????? ??????? ???????? ?' ???? ????? ????.[3]
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[????? ??? ???? | ?????]???? ??????? ??????? ?? ??? ??? ????? ??????????, Ki ?-Ki'?, ?????? ??????? ?????-???????, ??????. ???? ????-????? Ki ???? ?????? ????? ???? ??????? ???? ?????; ???? ?????? ?????? ??? ??????? ?????????? ????????? (Isothermal Titration Calorimetry; ITC), ??? ????? ????? ?????? ?? ?????, ????? ???? ??????? ?? ?????.[4] ????? ???, ???? ??????????? Ki'? ??? ?????? ?????, ???? ?????? ??????-??????? ?????? ?? ??? ???, ????? ????? ????? ?????? ?????. Ki'? ???? ???? ????? ?? ????? ???? ???, ?? ??? ????? ?? ??????? ????????? ???????? ????? ?? ???? ????????, ?????? ???????[5] ??????? ???????-???? ??????:
??? ???????? ???????? α ?-α' ?????? ?? ??? ????? ????? ???? ????? ??????????? ???:
?????, ??????? ????? ?-Km ??-Vmax ?????????? ?? ?????? ?????? ?-(α/α')Km ?-(1/α')Vmax, ??????. ?? ???, ?????? ???????-???? ??????? ????? ???????? ????? ?????? ????? ?????? ????, ??? ????? ????? ????? ???? ???? ??????? ???? ????? ?????????? ?????? ??????????. ?????? ???, ???? ???? ???? ????? ????? ????? ????? ????? ?? ???? (??? ????); ?? ???, ????? ??????? ????? ????? ?? ?-Ki'? ????? ????? ?? Ki ???? ????? ???? ????.
?????? ?????? ?????? ?? ?????? ?????? ?? ?????? ???????? ????? ????? ??????? ????? ???? ?? ?????? ???????-????, ?????? ???? Lineweaver-Burk ?? ???? Eadie-Hofstee. ?? ????, ?????? Lineweaver-Burk ??????? ?????, ???? ?????? ??????? ?????? ?? ??? ?-y, ??? ?????? ??????? ??? ???? ??????? ?? ?-Vmax. ????? ????, ???? ?????? ??? ?????? ?????? ?? ??? ?-x ????? ?????, ??? ????? ??????? ??? ?? ??????? ?? ?-Km. ?? ???, ??? ????? ????? ????? ?? ?-Ki ??-Ki'? ?????,[6] ?? ?????? ?????? ??? ??????? ??????? ????? ?????? ?? ???????? ??????? ????, ?????? ????.
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[????? ??? ???? | ?????]- ??????? ?? ????? ?????? ???? ???? ??? ?? ?? ??????, ???? ??? ?????? ?-EIS ??? ?????? ???????, ?????? ????? ????? ???? ?? ?? ????? ???? (?????????? ??????? ?????) ??? ?? ????? ?????-??????? (ES). ????? ???? ???? ???? Vmax ???? ????, ?? ??? ?-Km ???? ?????.[7]
- ????? ???? ?????? (Uncompetitive) - ????? ???? ????? ???? ?????? ??????-??????? (ES), ?? ?? ???????? ???????; ??????? ?-EIS ?? ???? ???????. ??? ????? ?? ???? ????? ?????? ?? ?-Vmax ??? ?-Km.[7]
- ????? ??????? ????? - ????? ??? ???????? ?? ????? ?? ?????? ?????? ?? ?????? ??????. ????? ???? ???? ?????? ??????? ?? ????? ??????, ?? ?????? ?? ?????. ?????? ??????? ?? ????? ?????????? ??????? ??????? ??????? ??????. ?? ???? ?????? ?? ???? ??? ????? ????? ??????? ??????. ??????? ??????? ??????, ???? ??? ???????? ?????? ???? ?????? ?????? ??????? ?????. ???? ???????? ??????, ??? ?????? ???? ???? ????, ????? ?? ??????.[8] ????? ????? ?? ??? ????? ??? ?????? ?????? ????? ?????? ????????? ?????? ??? ???? ????? ???? ?? ???? ?????.
- ????? ????-??? (Slow-tight inhibition) - ????? ???? ?????? ??????? ?? ?????? ?????? EI ???? ????????? ?????? ??? ??? ???? EI*, ?? ????? ?????? ????? ????. ????? ?? ???? ?????? ????? ?????? ??????. ??? ????? ???, ??????? ???????-???? ??????? ????? ??? ???? ?? Ki, ????? ????. ???? ?????? ?? ?-Ki ???? ?????? ??? ?????? ?????? ???? ?? ???? Kon ????? Koff ?? ?????????? ?????. ????? ???? ??? ???? ?? ????? ?? ????.
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???? ???????? ?????? ????? ?? ???????? ???? ??????, ???? ????? ???????? ??????? ?????? ???? ????? ?? ????????, ??? ?? ????? ?? ?? ????? ???? ????? ?? ??? ??????? ??? ????? ?????????? ?? ?????. ????? ?"?????? ???????" ??? ?? ????? ??????, ????? ?????? ?????? ?? ?????? ?????? ???? ??????? (Antiretroviral drugs) ??????? ?????? ?-HIV.[9] ?????????, ???? ?????? ?????? ?? ????? ????? ????? ????? ???????? ???? ?????. ???? ?????? ?? ???? ?????? ???? ??????? ?? ?????? ?-HIV, ??? ????? ?? ??????? ?? ???? ????? ?? ??????. ????? ??????? ?????? ?????? ?????? ??? ??????? ???? ????? ?? ??? ?????? ?? ????? ??????-?????. ?? ????? ?????? ???? ?? ????? ????? ????? ?? ??? ????? ???? ???????? ????? ???? ???? (Ki ???? ????) ???? ?????? ?????? ????????. ????? ????? ??? ???? ???? ??? ?????? ????????????? ??????????; ????? ?? ???? ?? ???? ????? ?? ???? ??? ?????????? ?????? ?????? ???????? ??????????.

?? ???, ?? ?? ??????? ??????? ?? ???? ?? ?????????. ????, ????? ?? ???? ?????? HIV ??? ????????? (Tipranavir) ????? ?????. ??????? ?? ???? ?????? ?? ????? ???? ?? ????? ???? ???? ???????? ?????. ?????? ?? ??????? ??? ?????? ????? ?????? ???? ??????? ??????? ????? ???????, ????? ??? ???? ????????? ????? ?????? ??? ????? ???? ???? ??? ??????? ?????? ???.
?????? ?????? ???? ????? ?? ?????? ?????????? ?????? ?????? ?????? ?????. ??????, ??? ???????? ?? ?????? ????? ?? ???? ????? ?????? ?????? ?-ATP, ??? ?????????? ?? ??????? ???. ?????? ??? ?????? ???????? ?????? ?????? ??????? ???????? ?????? ?? ATP ???. ?????? ????? ?????? ????? ??????? ?? ?? ??? ????? ????? ?????? ???? ???????? ?????? ?? ?????? ?????????? ????, ???? ???????? ?????? ???? ???? ???????? ?????? ????? ???? ????? ?-ATP. ?????? ???, ?? ??? ?????? ?? ?????? ????? ?????? ????? ???? ????? ?? ??????? ????, ?? ?? ??? ??? ???? ??????? ?-ATP, ?? ????? ??????? ???? ?????? ?? ?????? ???? ?? ?????? ????? ????? ????.[10]
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????? ???? ???? ???? ?????????????? ???? ????? ?? ?????. ?????? ???? ?????? ?? ???????? ???? ??? ???? ??? ?? ?????, ??? ??????? ?? ?? ????????; ?? ?? ?????? ??????? ??? ???? ?????? ??? ??????? ????? ?????? ?? ???? ????? ?? ?????. ??????, ????? ???????? ?? pH ????????? ?????? ???? ??? ????????? ?? ?? ???? ??????, ?? ???? ????? ?? ???????. ????? ????, ??? ??????? ?????? ?? ???????? ?????? ?? ???? ??????; ???? ????? ??????????? ?????? ????? ?????????? ?? ?????? ???????? ?????? ?? ???????? ?????, ???????? ?????? ????? ???????.[12]
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????? ????? ?????, ?????? ???? ?????? ?????? ????? ?? ??????? ???? ?? ?????? (EI) ?? ?? ????? ??????-??????? (ESI) ??? ?????? ?????? ??? ???? ????? ???? ????? ???????, ????? ??? ????? ??? - EI*. ???? ??? ???? EI* ???? ??? ?????????????? ?? kinact. ???? ??????? EI ????? ??????? ?? ES, ????? ?? ?????? ???? ?????? ????? ?????? ?? ??? ????? ?? ??????? ?? ?????? ?? ???? ???, ????. ???? ???? ?? ??? ????? ???? ?????? ??????? ?? ???? ???? ???? ?? ???? ?????.
???? ?????? ??????????????? ?? ????? ?? ?????? ??????? ???? ?????? ?? ???? ?????? ???? ??????? ?????? ????? ????. ??????? ???? ????? ???? ????, ???? ??? ?? ?? ????? ?????????????. ????? ?????? ??? ??????? ???? ????? ?? ??? ??????????? ?????? ?? ?? ????. ????? ?? ???? ???????? ????? ?? ????. ?? ????? ???? ?? EI ?????, ??? ??????????? ???? ?? ????? ?????? ????? ???? ?????? kinact ?-Ki[13]
???? ????? ?????? ?????? ???? ???????? ??? ??? ???????????? ????. ????? ??, ????? ?????? ?? ???? ?? ?????? ??? ??? ????? ??? ?????? ??? ???? ????? ?? ?????? ???? ?????? ?????? ?? ???? ????? ?? ???????????? ?? ??????. ?? ???? ???? ??? ??????? ????????? ??? MALDI-TOF. ????? ??????, PMF? (Peptide mass fingerprinting) ????? ????? ?? ?????? ???? ?????? ????? ???? ?????, ??????? ?????? ???? ???????. ????? ?? ?????? ???? ???? ?? ??????? ????? ???? ????? ?????? ??????? ????????? ???. ?????? ?????? ????? ???? ?????? ?? ????? ???? ?? ??? ?? ?? ??? ??????.
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?? ?? ????? ???????? ????? ?????? ?????? ????? ???????? ?? ????? ?????? ????. ???? ?????? ?????? ??????? ?? ??? ??????? ????? ????, ?? ??? ?? ????? ??????? ????? ??????? ???? ??????. ??????? ??????? ?? ??? ?????? ?????? ??????? ???? ??? ?? ?????? ???????? ???? ??????. ?????? ???, ??? ???????? ???? ?????? ??????? ?????? ?????? EI ?? ??????? ????? ?????? ?? ???? ?? ????? ???? ???? ?????? EI* ?? ??? ??? (??? ???? ????). ??????? ?????? ?? ????? ?????-???? (slow-binding). ?????? ????? ???? ???? ?????? ?????? ?????? ???? ?????? ??????????. ??? ???????? ??????? ??????? ?????-???? ????? ??? ?????? ?????? ??? ????????,[14] ??????????,[15] ?????? ???????? ?? ?????????.[16]
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?????????????????????? (DFP) ???? ?????? ???? ??? ???? ?????? ????? ?????? ???? ????. ?????? ???? ????????? ?? ???? ????-?????? ?-DFP, ?? ????? ????? ????? ????? ????? ???? ?????, ?????? ?? ???????. ????? ????, ?-DFP ???? ?? ?? ???? ????? ?? ?????????? ?????? ??????? ?? ?????????, ??????? ??? ??? ??????????? ???, ??????? ?????? ??? ???? ?-100 ?"?.
????? "????????" (Suicide inhibition) ??? ??? ?? ???? ?? ????? ???? ???? ??? ?????? ???? ?? ????? ????? ????????? ???? ????? ???. ????? ??? ??? ????? ?? ???????? ?? ????????, α-??????????????????? ?? DFMO, ??? ???? ?????? ??????? ????????, ????? ?????? ????? ?????. ?????? ???????? ???????????? ???? ???? ?? ????? ??????????? ?? DFMO ????? ????????. ?????, ????? ????? ??????????? ?????? ????? ???? ???????, ????? ?? ?????? ??????? ??? ??????, ?????????? ????. ???? ????????? ?? ?? DFMO ????? ?? ?? ????? ?????? ?? ????? ???? ????? ?????? ???? ????? ?? ??????.
???? ?????? ???? ???? ???? ?????? ?????? ????? ??????? ?? ???? EI ?? ???????, ?????? ????? ?????? ????? ?????? ????? ????? ???. ????, ????? ????? ?? ?????? ?????????? ??????? ?????? ??? ??? Trypanosoma cruzi, ???? ??? ???????? ?? ????? quinacrine mustard, ??????? ???? ????? ???. ???????? ??????? ????? ????? ?????, ?? ??????? ????? ???????? ???? ?????? ?? ????? ????? ?????? ??? ????? ?????-???? ???.
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?????? ????? ?? ???? ?? ????? ????? ????, ???? ?????? ???????? ?? ??? ?????? ?????? ????? ?? ???? ????? ???. ????, ???? ?????? ?????? ?????? ????? ??? ????? ??????? ????? ??????: ????? ???? ???? ?? ??????? ??? ????? ???? ?????? ?????? ?????? ????????. ???? ????? ?????? ?? ????? ??????, ??? ?????? ?? ??? ?????? ???????????? ??? ?????? ???? ???? ?? ??????? ??????????? ????? HTC ?(High-throughput screening) ?????? ????? ?? ?????? ?????? ?????? ????? ????? ?????? ????????.
??????? ?????? ?? ???? ?????? ??? "Rational drug design", ??? ???? ????? ????? ????????? ?? ???? ????? ?? ????? ??? ????? ???? ???????? ?????? ????? ???????. ???? ??? ?????? ?????? ???, ???? ?? ???????? ??????? ????? ????? ???? ???. ????? ???? ???? ?? ??? ????? ????? ?? ????? ?? ?????? ?????? ?????-???? ??? ????? ?? ??? ????? ???????? ???? ?????. ???? ?? ???? ?? ??????? ??????? ????? ??????? ????? ????? ?????????. ????? ????? ?????? ?? ???? ?? ?????? ???? ??? ????? ?????. ???? ????? ?? ????? ?????? ???? ?? ???? ?????????? ?? <10-9 ????[17]
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[????? ??? ???? | ?????]????? ??????? ?????? ???? ??????? ?????? ??????????? ??????????. ????? ??????? ???? ?? ?????? ?????? ????? ??????? ??????? ??? ???? ?? ??? ?? ?? ??? ???? ???? ????. ????? ?????? ??? ?????? ??? ????????? ??????? ????? ??????? ????. ?????? ????????? ?????? ?????? ?????? ???????, ?? ?? ??????? ?????, ?????? ??????, ?? ??????? ????? ?????, ?????? ???????, ?? ?????? ?????, ?????? ????????.

?????? ????? ????? ?????? ??????? ??? ??????? ?????? ??????. ???? ??????? ??? ??????? ???? ????? ????? ????? ???? ??? ???????. ??? ???????? ???????? ?? ??????? ?? ??????? ?????? ??? ????? ?? ????? ????? ??????? ???. ??????, ?????? ????-????????? ????? ?????? ????? ??????? ????? ?? ????? ?? ???? ??????. ?????? ???? ??????? ?? ??????? ?????? ????. ?????? ????? ?????? ?? ????? ????? ????? ???????, ???? ????? ????? ?? ?????? ??????.
????? ????? ??????? ????? ?????? ??? ???????? (??????), ????? ?????? ?????? ???? (??? ????). ?????? ?? ??? ???? ??? ?? ?????? cGMP, ???????????? ?????? ??? 5, ??? ????? ?? ???????? ?? ???????? cyclic guanosine monophosphate.[18] ???? ??????? ????? ??????? ??????? ????? ???? ??? ??????? ??? ????? ???? ??????? ????? ?? ????, ??? ????? ???????. ???? ??????? ?????? ?? ??????? ?? ?????? ????? ?? ??????, ??? ?????? ?? ??? ?????? ???? ???? ????.

????? ????? ?????? ????? ?? ??? ???????? ?????????? ?? ?????? ????? ????, ????? ????? ?????? ?? ?????? ???????? ?????? ?????. ????? ????? ??? ????? ???????? ?? ???????? ?? ?????? ??-?????-????? ???????, ????? ?????? ?????? ?? ??? ????????. ???????? ???? ?? ?????? ?????? DHFR, ??? ??? ?? ???? ?? ?????????? ?? ????????. ????? ?? ?? ?????????? ?? ????????? ??, ??? ????? ????? ??????? ????? ?????? ???????, ???? ?????? ?????? ???? ????? ????????? ?????????? ?????? ?????.[19]

?????? ?????? ?? ?????? ??????? ???????? ????????? ?? ???????. ????, ??????? ?????? ????? ?? ??? ????? ??????? ???? ???, ???????????. ?????? ??????????? ????, ?????? ???????? ???????????, ?????? ?? ???????? ??????? ?? ????? ?????? ??? ?? ??????? ?????? ??. ?? ?????? ?????? ??? ?????? ????? ?? ???? ??? ????? ??????. ????? ????? ??????? ?? ???????? ?????? ??????, ??????????? ??????? Streptomyces R61.
????? ????? ????? ???? ???? ???? ???? ????? ????? ???????? ????? ???? ???? ?? ???? ????? ??????? ??? ??? ???. ?????? ????, ??? ??? ???? ?????? ???????????, ???? ?????? ?? ????? ?? ?????? ????? ??????? ????????. ?????? ???????? ????? ??????? ??????????? ?? ??????? ????? ?????? ????? ?????????? ????????, ?? ????? ??? ?? ?????? ?????? ????.
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[????? ??? ???? | ?????]?????? ??????? ???? ?????? ?? ????? ???????. ??????? ???????? ???? ??? ??????? ?? ??? ????????? ??????? ?? ??????? ????????? ??? ??????? ???????? ?? ??????? ????? ???????. ????? ??? ??? ???????? ????????? ?? ??????????. ????? ?????? ?? ???? ?????? ?????? ATP, NADH ???????. ??? ????? ???????? ?? ????????? ??? ????? ?????? ?????? ??????? ?? ??? ???????????????-1 (PFK1). ????? ?-ATP ????, ??? ???? ???? ??????? ?-PFK1, ???? ????? ?? ??? ????? ??????; ?????????? ?????? ?????? ?-ATP ?????. ???? ???? ????? ?? ?????? ??????? ????? ???? ?? ATP ???. ?? ??????? ???????? ???? ??????? ?? ??????? ?????, ??? ???? ????? ?????? ?? ??????????? ?? ??????. ????? PFK1, ??????? 2,6-????????, ??????? ADP ?? ??????? ?????????? ??? ??????? ?????????.[20]
????? ????? ????????? ???? ????? ???? ?? ??????? ?????? ???????? ???????. ????? ???? ????? ?????, ?????? ???????? (??????? ???? ???? ????), ?????? ????? ??????? ???? ?????. ??? ??? ?????? ??????? ?? ??? ?????? ???????, ?? ????? ?????? ?????? ?????? ???????? ????? ??? ????? ?????? ???? ?? ????. ??? ?????? ????????? ????? ???????? ??? ????? ?? ????? ???? ??????? ?????? ???? ?????. ???? ?? ???? ?????? ???????? ????? ?? ???????, ????? ????? ????? ?????.[21] ?? ?? ????? ???????? ??? ?????, ??? ???? ???? ????????? ???????? ?? ??? ???????, ???? ???? ??? ??????? ????? ??? ????? ????? ?? ??????? ?????? ??????? ??? ?????.[22] ????? ????? ?????? ????? ????? ????????? ??? ???? Barstar ?? ??????????? ??????? Barnase.[23]
????? ??????
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???? ???? ?????? ????? ????? ????? ????? ??? ?? ?????? ??????, ??? ????????? ????????, ??????? ???????? ???????? ????? ???????. ?????? ?????? ?? ???? ??? ???????? ???????? ?????, ??????? ????? ?????? ?????? ???? ???????? ?????????.[24] ???????? ????????? ??????? ??????? ????? ?????? ?????? ?? ?? ??????? ???????? ????????, ??? ?? ????? ?? ???????, ????? ???????? ?????? ??????? ???. ??????, ???????? (?????), ???? ??????? ??????? ?????? ???? ?????, ????? ?????? ??????? ?? ??????? ?????? ?? ?????? ????????????? ???? ???.[25]
????? ?????? ???? ?????? ?????????????? ??????? ????? ?????? ?????? ?????, ??????? ????? ??? ?????? ?? ???? ??????? ???. ??? ??????? ?????? ???, ??? ??????? ??????? ????, ?? ???? ??? ???????? ?????? ???????? ???????.[26] ????? ???????????? ??? ???????????????, ????? ????? ??????? ?????? ????????, ??? ????? ?????? ?????????? ??????. ????? ?? ????? ?? ???? ?????? ???? ?????? ??????????????? ??????????, ?????? ??????, ??? ?????. ???????????? ????? ?????? ?? ?????? ?????? ?? ???????. ??????, ??????? ??????? ??????, ?????? ?????????? ?????? ?? ?????? ?????????? ??????????.[27]
?? ?? ?? ?????? ?????? ???? ?? ????????? ????????, ????? ??? ?????? ?? ??????? ????????. ????? ?????? ???? ??? ???? ??????? ????? ??????? ????? ????? (Amanita). ??? ???? ????? ??? ????? ??????? RNA ???????? II ?????? DNA.[28] ?? ????? ??????????? (microcystin) ?????? ?? ??? ??????? ??? ????? ???? ???? ?? ?????? ?????????.[29] ??? ?? ???? ???? ????? ??? ???? ????? ????, ??? ???????? ????, ????????? ?????? ???? ????? ?? ?????? ???? ???? ??????.[30]
?? ??????? ?????? ????? ????? ??????, ?????? ????? ??????? (??? ????) ??????? ???? ??????. ????? ???? ????? ?? ????? ?????? ??? ??????? ??????: ?? ?????? ??????? ???? ?????? ?? ????? ???????? ????, ??????? ??????? ????? ???? ?? ?????? ???????? ????. ????? ??? ??? ??????, ???? ????? ???? ?????? ????? ?????? ???? ?? ???? ??????. ????? ?? ??? ????????? ?????? ?????? ????????? ???? ?????. ???? ?????? ??? ???? ???? ???? ??????, ?? ???????? ????? ??? ??? ????? ??.[31]
??????? ????????
[????? ??? ???? | ?????]- ????? ???????? ?? ????? ???????, ?? ?"? ??? ????' ??????????? ??????, ???? ?????? ?????????.
- ????????? ???????????? ???????? ????????, ?????? ?? ???? ?????????? ?? ?????? ????????? ????????? (NC-IUB) ?? ??????????? ????? ???????.
- PubChem from NCBI, ???? ?????? ?? ?????? ?????? ???????.
- BRENDA, ??? ?????? ?? ??????? ?????? ?????? ?????? ?? ?? ??? ???.
????? ??????
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