全文获取类型
收费全文 | 110篇 |
免费 | 5篇 |
出版年
2022年 | 3篇 |
2021年 | 2篇 |
2019年 | 1篇 |
2017年 | 1篇 |
2015年 | 1篇 |
2014年 | 3篇 |
2013年 | 3篇 |
2012年 | 12篇 |
2011年 | 6篇 |
2010年 | 3篇 |
2009年 | 2篇 |
2008年 | 8篇 |
2007年 | 11篇 |
2006年 | 9篇 |
2005年 | 6篇 |
2004年 | 9篇 |
2003年 | 5篇 |
2002年 | 4篇 |
2001年 | 2篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1966年 | 1篇 |
1965年 | 2篇 |
1964年 | 1篇 |
1962年 | 2篇 |
1959年 | 1篇 |
1958年 | 3篇 |
1957年 | 1篇 |
1955年 | 3篇 |
1946年 | 1篇 |
1937年 | 1篇 |
排序方式: 共有115条查询结果,搜索用时 234 毫秒
81.
Machius M Declerck N Huber R Wiegand G 《The Journal of biological chemistry》2003,278(13):11546-11553
It is generally assumed that in proteins hydrophobic residues are not favorable at solvent-exposed sites, and that amino acid substitutions on the surface have little effect on protein thermostability. Contrary to these assumptions, we have identified hyperthermostable variants of Bacillus licheniformis alpha-amylase (BLA) that result from the incorporation of hydrophobic residues at the surface. Under highly destabilizing conditions, a variant combining five stabilizing mutations unfolds 32 times more slowly and at a temperature 13 degrees C higher than the wild-type. Crystal structure analysis at 1.7 A resolution suggests that stabilization is achieved through (a) extension of the concept of increased hydrophobic packing, usually applied to cavities, to surface indentations, (b) introduction of favorable aromatic-aromatic interactions on the surface, (c) specific stabilization of intrinsic metal binding sites, and (d) stabilization of a beta-sheet by introducing a residue with high beta-sheet forming propensity. All mutated residues are involved in forming complex, cooperative interaction networks that extend from the interior of the protein to its surface and which may therefore constitute "weak points" where BLA unfolding is initiated. This might explain the unexpectedly large effect induced by some of the substitutions on the kinetic stability of BLA. Our study shows that substantial protein stabilization can be achieved by stabilizing surface positions that participate in underlying cooperatively formed substructures. At such positions, even the apparently thermodynamically unfavorable introduction of hydrophobic residues should be explored. 相似文献
82.
Crystal structure of the 47-kDa lipoprotein of Treponema pallidum reveals a novel penicillin-binding protein 总被引:4,自引:0,他引:4
Deka RK Machius M Norgard MV Tomchick DR 《The Journal of biological chemistry》2002,277(44):41857-41864
Syphilis is a complex sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum. T. pallidum has remained exquisitely sensitive to penicillin, but the mode of action and lethal targets for beta-lactams are still unknown. We previously identified the T. pallidum 47-kDa lipoprotein (Tp47) as a penicillin-binding protein (PBP). Tp47 contains three hypothetical consensus motifs (SVTK, TEN, and KTG) that typically form the active center of other PBPs. Yet, in this study, mutations of key amino acids within these motifs failed to abolish the penicillin binding activity of Tp47. The crystal structure of Tp47 at a resolution of 1.95 A revealed a fold different from any other known PBP; Tp47 is predominantly beta-sheet, in contrast to the alpha/beta-fold common to other PBPs. It comprises four distinct domains: two complex beta-sheet-containing N-terminal domains and two C-terminal domains that adopt immunoglobulin-like folds. The three hypothetical PBP signature motifs do not come together to form a typical PBP active site. Furthermore, Tp47 is unusual in that it displays beta-lactamase activity (k(cat) for penicillin = 271 +/- 6 s(-1)), a feature that hindered attempts to identify the active site in Tp47 by co-crystallization and mass spectrometric techniques. Taken together, Tp47 does not fit the classical structural and mechanistic paradigms for PBPs, and thus Tp47 appears to represent a new class of PBP. 相似文献
83.
84.
85.
Haines DC Hegde A Chen B Zhao W Bondlela M Humphreys JM Mullin DA Tomchick DR Machius M Peterson JA 《Biochemistry》2011,50(39):8333-8341
Identifying key structural features of cytochromes P450 is critical in understanding the catalytic mechanism of these important drug-metabolizing enzymes. Cytochrome P450BM-3 (BM-3), a structural and mechanistic P450 model, catalyzes the regio- and stereoselective hydroxylation of fatty acids. Recent work has demonstrated the importance of water in the mechanism of BM-3, and site-specific mutagenesis has helped to elucidate mechanisms of substrate recognition, binding, and product formation. One of the amino acids identified as playing a key role in the active site of BM-3 is alanine 328, which is located in the loop between the K helix and β 1-4. In the A328V BM-3 mutant, substrate affinity increases 5-10-fold and the turnover number increases 2-8-fold compared to wild-type enzyme. Unlike wild-type enzyme, this mutant is purified from E. coli with endogenous substrate bound due to the higher binding affinity. Close examination of the crystal structures of the substrate-bound native and A328V mutant BMPs indicates that the positioning of the substrate is essentially identical in the two forms of the enzyme, with the two valine methyl groups occupying voids present in the active site of the wild-type substrate-bound structure. 相似文献
86.
87.
88.
Eph receptors and their membrane-bound ligands are intimately involved in the control of morphogenic processes during embryonic development and adult tissue homeostasis. By their ability to orchestrate cell migration, pattern formation and tissue integrity they are also prone to be involved in carcinogenic growth. In this review we concentrate on their involvement in the normal and carcinogenic development of the breast. In this context we summarize their multi-faceted functions as tumor suppressors, tumor promoters, angiogenic inducers and regulators of stem cell homeostasis. 相似文献
89.
90.