全文获取类型
收费全文 | 1093篇 |
免费 | 75篇 |
出版年
2022年 | 8篇 |
2021年 | 12篇 |
2019年 | 6篇 |
2018年 | 8篇 |
2017年 | 7篇 |
2016年 | 17篇 |
2015年 | 23篇 |
2014年 | 34篇 |
2013年 | 86篇 |
2012年 | 49篇 |
2011年 | 56篇 |
2010年 | 28篇 |
2009年 | 33篇 |
2008年 | 61篇 |
2007年 | 67篇 |
2006年 | 73篇 |
2005年 | 77篇 |
2004年 | 49篇 |
2003年 | 48篇 |
2002年 | 63篇 |
2001年 | 26篇 |
2000年 | 17篇 |
1999年 | 18篇 |
1998年 | 22篇 |
1997年 | 21篇 |
1996年 | 14篇 |
1995年 | 15篇 |
1994年 | 8篇 |
1993年 | 3篇 |
1992年 | 20篇 |
1991年 | 7篇 |
1990年 | 11篇 |
1989年 | 11篇 |
1988年 | 14篇 |
1987年 | 17篇 |
1986年 | 9篇 |
1985年 | 7篇 |
1984年 | 19篇 |
1983年 | 10篇 |
1982年 | 16篇 |
1981年 | 6篇 |
1980年 | 5篇 |
1979年 | 4篇 |
1978年 | 6篇 |
1977年 | 8篇 |
1976年 | 5篇 |
1975年 | 3篇 |
1974年 | 4篇 |
1966年 | 4篇 |
1965年 | 5篇 |
排序方式: 共有1168条查询结果,搜索用时 31 毫秒
991.
992.
993.
Our current knowledge of protein unfolding is overwhelmingly related to reversible denaturation. However, to engineer thermostable
enzymes for industrial applications and medical diagnostics, it is necessary to consider irreversible denaturation processes
and/or the entire quaternary structure. In this study we have used lactate oxidase (LOD), which is employed in lactic acid
sensors, as a model example to design thermostable variants by rational design. Twelve mutant proteins were tested and one
of them displayed a markedly greater thermostability than all the mutants we had previously obtained by random mutagenesis.
This mutant was designed so as to strengthen the interaction between the subunits and stabilize the quaternary structure.
Since LOD is difficult to crystallize, its three-dimensional structure remains unknown. This study shows that it is possible
to carry out rational design to improve thermostability using a computer-aided quaternary structure model based on the known
tertiary structure of a related protein. Critical factors required for increasing the thermal stability of proteins by rational
design, where the 3-D structure is not available, are discussed.
Revisions requested 18 August 2005; Revisoins received 6 September 2005 相似文献
994.
Nagao J Aso Y Sashihara T Shioya K Adachi A Nakayama J Sonomoto K 《Bioscience, biotechnology, and biochemistry》2005,69(7):1341-1347
Nukacin ISK-1 is a type-A(II) lantibiotic produced by Staphylococcus warneri ISK-1. In this study, we characterized NukM and NukT, which are predicted to be involved in modification of prepeptide (NukA) and cleavage of leader peptide and subsequent secretion respectively. Localization analysis of NukM and NukT in the wild-type strain indicated that both proteins were located at the cytoplasm membrane. Interestingly, NukM expressed heterologously in St. carnosus TM300 was also located at the cytoplasm membrane even in the absence of NukT. Yeast two-hybrid assay showed that a complex of at least two each of NukM and NukT was associated with NukA. In vitro interaction analysis by surface plasmon resonance biosensor further suggested that membrane-located NukM interacted with NukA. These results indicate that NukM and NukT form a membrane-located multimeric protein complex and that post-translational modification of nukacin ISK-1 would occur at the cytoplasm membrane. 相似文献
995.
996.
997.
998.
999.
Hattori K Takamura F Tanaka A Takasugi H Taniguchi K Nishio M Koyama S Seki J Sakane K 《Bioorganic & medicinal chemistry letters》2005,15(13):3284-3287
A metabolism study of FR181157 (1) led to the discovery of new oxazole derivatives as active metabolites. The metabolite 6 with an epoxy ring exhibited high anti-aggregative potency with an IC(50) of 5.8 nM and potent binding affinity for the human recombinant IP receptor with a K(i) value of 6.1 nM and selectivity for human IP receptor over all other members of the human prostanoid receptor family. 相似文献
1000.
Hattori K Okitsu O Tabuchi S Taniguchi K Nishio M Koyama S Seki J Sakane K 《Bioorganic & medicinal chemistry letters》2005,15(13):3279-3283
Synthetic and biological evaluation of novel diphenyloxazole derivatives containing a pyrrolidine ring, as a prostacyclin mimetic without the PG skeleton, are described. Asymmetric reduction of a ketone using a chiral Ru complex and reductive amination by NaBH(4) produces four isomers of the tetrahydronaphthalene ring and the pyrrolidine ring with high stereoselectivity. FR193262 (4), (R,R)-diphenyloxazolyl pyrrolidine derivative, displays high potency and agonist efficacy at the IP receptor and has good bioavailability in rats and dogs. 相似文献