全文获取类型
收费全文 | 164篇 |
免费 | 14篇 |
国内免费 | 14篇 |
专业分类
化学 | 182篇 |
晶体学 | 1篇 |
综合类 | 1篇 |
物理学 | 8篇 |
出版年
2022年 | 11篇 |
2021年 | 11篇 |
2020年 | 3篇 |
2019年 | 2篇 |
2018年 | 3篇 |
2017年 | 6篇 |
2016年 | 11篇 |
2015年 | 2篇 |
2014年 | 8篇 |
2013年 | 13篇 |
2012年 | 9篇 |
2011年 | 7篇 |
2010年 | 9篇 |
2009年 | 5篇 |
2008年 | 11篇 |
2007年 | 5篇 |
2006年 | 9篇 |
2005年 | 9篇 |
2004年 | 6篇 |
2003年 | 13篇 |
2002年 | 2篇 |
2001年 | 4篇 |
2000年 | 8篇 |
1999年 | 5篇 |
1998年 | 2篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1991年 | 1篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有192条查询结果,搜索用时 15 毫秒
1.
The serine protease, DegP exhibits proteolytic and chaperone activities, essential for cellular protein quality control and normal cell development in eukaryotes. The P. falciparum DegP is essential for the parasite survival and required to combat the oscillating thermal stress conditions during the infection, protein quality checks and protein homeostasis in the extra-cytoplasmic compartments, thereby establishing it as a potential target for drug development against malaria. Previous studies have shown that diisopropyl fluorophosphate (DFP) and the peptide SPMFKGV inhibit E. coli DegP protease activity. To identify novel potential inhibitors specific to PfDegP allosteric and the catalytic binding sites, we performed a high throughput in silico screening using Malaria Box, Pathogen Box, Maybridge library, ChEMBL library and the library of FDA approved compounds. The screening helped identify five best binders that showed high affinity to PfDegP allosteric (T0873, T2823, T2801, , CD00811) and the catalytic binding site (T0078L, T1524, T2328, BTB11534 and 552691). Further, molecular dynamics simulation analysis revealed RJC02337, BTB11534 as the best hits forming a stable complex. WaterMap and electrostatic complementarity were used to evaluate the novel bio-isosteric chemotypes of RJC02337, that led to the identification of 231 chemotypes that exhibited better binding affinity. Further analysis of the top 5 chemotypes, based on better binding affinity, revealed that the addition of electron donors like nitrogen and sulphur to the side chains of butanoate group are more favoured than the backbone of butanoate group. In a nutshell, the present study helps identify novel, potent and Plasmodium specific inhibitors, using high throughput in silico screening and bio-isosteric replacement, which may be experimentally validated. RJC02337相似文献
2.
Henriques ES Floriano WB Reuter N Melo A Brown D Gomes JA Maigret B Nascimento MA Ramos MJ 《Journal of computer-aided molecular design》2001,15(4):309-322
We present the search for a new model of -factor XIIa, a blood coagulation enzyme, with an unknown experimental 3D-structure. We decided to build not one but three different models using different homologous proteins as well as different techniques and different modellers. Additional studies, including extensive molecular dynamics simulations on the solvated state, allowed us to draw several conclusions concerning homology modelling, in general, and -factor XIIa, in particular. 相似文献
3.
JinTangDU YahMeiLI ZhongZhouCHEN ShiZhongLUO YuFenZHAO 《中国化学快报》2005,16(7):856-858
O-Phosphoryl serine derivative can perform serf-catalytic esterification reaction in the mixture of CH3OH and CHCl3 at the room temperature. The phosphoryl group participation was the key step of the esterification. This type of reactions were proposed through an intermediate of mixed phosphoric-carboxylic anhydride that might provide a clue to the function of the phosphoryl group in the phosphorylated enzymes and in the prebiotic synthesis of protein. 相似文献
4.
The application of hydrolases in organic solvents for synthetic purposes is a procedure routinely adopted in organic chemistry, especially for the preparation of chiral building blocks. Numerous studies have shed light on several aspects of the mechanism of hydrolase action in low-water environments. Procedures suitable to improve the catalytic efficiency of enzymes and productivity of the synthetic processes have been reported. These fundamental and applied investigations have made hydrolase-catalyzed reactions in organic solvents of industrial interest. In this article we describe and discuss various approaches adopted to optimize the performance of hydrolases in organic media, with special emphasis on the formulation of the biocatalysts which, under proper conditions, can display an activity equal to that displayed in aqueous buffers. 相似文献
5.
We have developed an affinity-based probe for the proteomic profiling of aspartic proteases. Our probe was shown to be selective towards aspartic proteases over other proteins. It was also shown that the strategy may be used to label selectively aspartic proteases in the presence of a large excess of other proteins, thus making it useful for future proteome profiling experiments. 相似文献
6.
7.
Summary 2-Benzoylamino-6,7-dimethoxy-4H-3,1-benzoxazin-4-one was prepared by thermal treatment of 2-(3-benzoylthioureido)-4,5-dimethoxybenzoic acid and by benzoylation of 2-amino-6,7-dimethoxy-4H-3,1-benzoxazin-4-one. The inactivation of chymotrypsin and human leukozyte elastase by the title compound and 2-benzoylamino-4H-3,1-benzoxazin-4-one is reported.
2-Benzoylamino-6,7-dimethoxy-4H-3,1-benzoxazin-4-on: Synthese und Untersuchung der Inaktivierung von Serin-Proteasen
Zusammenfassung 2-Benzoylamino-6,7-dimethoxy-4H-3,1-benzoxazin-4-on wurde durch thermische Behandlung von 2-(3-Benzoylthioureido)-4,5-dimethoxybenzoesäure und durch Benzoylierung von 2-Amino-6,7-dimethoxy-4H-3,1-benzoxazin-4-on hergestellt. Über die Inaktivierung von Chymotrypsin und humaner Leukozyten-Elastase durch die Titelverbindung und 2-Benzoylamino-4H-3,1-benzoxazin-4-on wird berichtet.相似文献
8.
Proteolytic antibodies appear to utilizecatalytic mechanisms akin to nonantibody serine proteases, assessed from mutagenesis
and protease-inhibitor studies. The catalytic efficiency derives substantially from the ability to recognize the ground state
with high affinity. Because the proteolytic activity is germline-encoded, catalysts with specificity for virtually any target
polypeptide could potentially be developed by applying appropriate immunogens and selection strategies. Analysis of transition-state
stabilizing interactions suggests that chemical reactivity ofactive-site serine residues is an important contributor to catalysis.
A prototype antigen analog capable of reacting covalently with nucleophilic serine residues permitted enrichment of the catalysts
from a phage-displayed lupus light-chain library. Further mechanistic developments in understanding proteolytic antibodies
may lead to the isolation of catalysts suitable for passive immunotherapy of major diseases, and elicitation of catalytic
immunity as a component of prophylactic vaccination. 相似文献
9.
Knowledge of chemical shift-structure relationships could greatly facilitate the NMR chemical shift assignment and structure refinement processes that occur during peptide/protein structure determination via NMR spectroscopy. To determine whether such correlations exist for polar side chain containing amino acid residues the serine dipeptide model, For-L-Ser-NH(2), was studied. Using the GIAO-RHF/6-31+G(d) and GIAO-RHF/TZ2P levels of theory the NMR chemical shifts of all hydrogen ((1)H(N), (1)H(alpha), (1)H(beta1), (1)H(beta2)), carbon ((13)C(alpha), (13)C(beta), (13)C') and nitrogen ((15)N) atoms have been computed for all 44 stable conformers of For-L-Ser-NH(2). An attempt was made to establish correlation between chemical shift of each nucleus and the major conformational variables (omega(0), phi, psi, omega(1), chi,(1) and chi(2)). At both levels of theory a linear correlation can be observed between (1)H(alpha)/phi, (13)C(alpha)/phi, and (13)C(alpha)/psi. These results indicate that the backbone and side-chain structures of For-L-Ser-NH(2) have a strong influence on its chemical shifts. 相似文献