全文获取类型
收费全文 | 230篇 |
免费 | 22篇 |
出版年
2023年 | 5篇 |
2022年 | 2篇 |
2021年 | 10篇 |
2020年 | 3篇 |
2019年 | 4篇 |
2018年 | 4篇 |
2016年 | 2篇 |
2015年 | 10篇 |
2014年 | 16篇 |
2013年 | 16篇 |
2012年 | 18篇 |
2011年 | 21篇 |
2010年 | 11篇 |
2009年 | 17篇 |
2008年 | 13篇 |
2007年 | 16篇 |
2006年 | 14篇 |
2005年 | 12篇 |
2004年 | 8篇 |
2003年 | 8篇 |
2002年 | 10篇 |
2001年 | 8篇 |
2000年 | 7篇 |
1999年 | 6篇 |
1992年 | 4篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1984年 | 1篇 |
排序方式: 共有252条查询结果,搜索用时 15 毫秒
51.
Electrostatic interactions are believed to play an important role in stabilizing the native structure of proteins. We have quantified the contribution to stability of an interaction between two oppositely charged side-chains on the surface of barnase. Using site-directed mutagenesis, glutamate 28 and lysine 32 were introduced onto the solvent-accessible side of the second alpha-helix in barnase. These two residues are separated by one turn of the helix, and so are ideally situated for their opposite charges to interact. Double mutant cycle analysis reveals that the interaction between Glu28 and Lys32 contributes only approximately 0.2 kcal/mol to stability of the protein. All other interactions between exposed charged side-chains in barnase examined so far also contribute little to stability. We explain this low value by their location on the surface, rather than in the interior, of the protein. 相似文献
52.
Falcipain-2, a papain family cysteine protease of the malaria parasite Plasmodium falciparum, plays a key role in parasite hydrolysis of hemoglobin and is a potential chemotherapeutic target. As with many proteases, falcipain-2 is synthesized as a zymogen, and the prodomain inhibits activity of the mature enzyme. To investigate the mechanism of regulation of falcipain-2 by its prodomain, we expressed constructs encoding different portions of the prodomain and tested their ability to inhibit recombinant mature falcipain-2. We identified a C-terminal segment (Leu155–Asp243) of the prodomain, including two motifs (ERFNIN and GNFD) that are conserved in cathepsin L sub-family papain family proteases, as the mediator of prodomain inhibitory activity. Circular dichroism analysis showed that the prodomain including the C-terminal segment, but not constructs lacking this segment, was rich in secondary structure, suggesting that the segment plays a crucial role in protein folding. The falcipain-2 prodomain also efficiently inhibited other papain family proteases, including cathepsin K, cathepsin L, cathepsin B, and cruzain, but it did not inhibit cathepsin C or tested proteases of other classes. A structural model of pro-falcipain-2 was constructed by homology modeling based on crystallographic structures of mature falcipain-2, procathepsin K, procathepsin L, and procaricain, offering insights into the nature of the interaction between the prodomain and mature domain of falcipain-2 as well as into the broad specificity of inhibitory activity of the falcipain-2 prodomain. 相似文献
53.
Tadeusz Włostowski Alicja Krasowska Aneta Salińska Monika Włostowska 《Biological trace element research》2009,131(3):291-297
The objective of this study was to examine relations between body iron (Fe) status and cadmium (Cd) accumulation in a small
rodent, the bank vole, caught from the wild population in late autumn (November) and early spring (March). The concentrations
of Fe in the liver, kidneys, and duodenum in the bank voles from the spring were only 30%, 60%, and 70%, respectively, of
those found in the animals from the autumn. An analysis of hematocrit and hemoglobin content of blood showed no significant
effect of the season, suggesting that the animals from the spring were not anemic. The exposure to dietary Cd (10 μg/g) for
7 days resulted in 70% higher accumulation of Cd in the liver and kidneys of the spring than autumn bank voles, and the concentration
of Cd in the duodenum was 3.5 times higher in the spring animals, despite the fact that relative Cd intake was significantly
higher in the autumn bank voles. The data indicate that seasonal changes of body Fe status occurring in the wild bank voles
may influence tissue accumulation of Cd. 相似文献
54.
55.
Helen M. Berman Paul D. Adams Alexandre A. Bonvin Stephen K. Burley Bridget Carragher Wah Chiu Frank DiMaio Thomas E. Ferrin Margaret J. Gabanyi Thomas D. Goddard Patrick R. Griffin Juergen Haas Christian A. Hanke Jeffrey C. Hoch Gerhard Hummer Genji Kurisu Catherine L. Lawson Alexander Leitner Andrej Sali 《Structure (London, England : 1993)》2019,27(12):1745-1759
56.
Stereochemical criteria for prediction of the effects of proline mutations on protein stability
下载免费PDF全文
![点击此处可从《PLoS computational biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Bajaj K Madhusudhan MS Adkar BV Chakrabarti P Ramakrishnan C Sali A Varadarajan R 《PLoS computational biology》2007,3(12):e241
When incorporated into a polypeptide chain, proline (Pro) differs from all other naturally occurring amino acid residues in two important respects. The phi dihedral angle of Pro is constrained to values close to -65 degrees and Pro lacks an amide hydrogen. Consequently, mutations which result in introduction of Pro can significantly affect protein stability. In the present work, we describe a procedure to accurately predict the effect of Pro introduction on protein thermodynamic stability. Seventy-seven of the 97 non-Pro amino acid residues in the model protein, CcdB, were individually mutated to Pro, and the in vivo activity of each mutant was characterized. A decision tree to classify the mutation as perturbing or nonperturbing was created by correlating stereochemical properties of mutants to activity data. The stereochemical properties including main chain dihedral angle phi and main chain amide H-bonds (hydrogen bonds) were determined from 3D models of the mutant proteins built using MODELLER. We assessed the performance of the decision tree on a large dataset of 163 single-site Pro mutations of T4 lysozyme, 74 nsSNPs, and 52 other Pro substitutions from the literature. The overall accuracy of this algorithm was found to be 81% in the case of CcdB, 77% in the case of lysozyme, 76% in the case of nsSNPs, and 71% in the case of other Pro substitution data. The accuracy of Pro scanning mutagenesis for secondary structure assignment was also assessed and found to be at best 69%. Our prediction procedure will be useful in annotating uncharacterized nsSNPs of disease-associated proteins and for protein engineering and design. 相似文献
57.
Almo SC Bonanno JB Sauder JM Emtage S Dilorenzo TP Malashkevich V Wasserman SR Swaminathan S Eswaramoorthy S Agarwal R Kumaran D Madegowda M Ragumani S Patskovsky Y Alvarado J Ramagopal UA Faber-Barata J Chance MR Sali A Fiser A Zhang ZY Lawrence DS Burley SK 《Journal of structural and functional genomics》2007,8(2-3):121-140
58.
Fernandez-Martinez J Phillips J Sekedat MD Diaz-Avalos R Velazquez-Muriel J Franke JD Williams R Stokes DL Chait BT Sali A Rout MP 《The Journal of cell biology》2012,196(4):419-434
The nuclear pore complex (NPC) is a multiprotein assembly that serves as the sole mediator of nucleocytoplasmic exchange in eukaryotic cells. In this paper, we use an integrative approach to determine the structure of an essential component of the yeast NPC, the ~600-kD heptameric Nup84 complex, to a precision of ~1.5 nm. The configuration of the subunit structures was determined by satisfaction of spatial restraints derived from a diverse set of negative-stain electron microscopy and protein domain-mapping data. Phenotypic data were mapped onto the complex, allowing us to identify regions that stabilize the NPC's interaction with the nuclear envelope membrane and connect the complex to the rest of the NPC. Our data allow us to suggest how the Nup84 complex is assembled into the NPC and propose a scenario for the evolution of the Nup84 complex through a series of gene duplication and loss events. This work demonstrates that integrative approaches based on low-resolution data of sufficient quality can generate functionally informative structures at intermediate resolution. 相似文献
59.
Rajput C Arif E Vibhuti A Stobdan T Khan AP Norboo T Afrin F Qadar Pasha MA 《Biochemical and biophysical research communications》2006,348(2):735-740
Sojourners visiting high-altitude (HA) (>2500 m) are susceptible to HA disorders; on the contrary, HA natives are well adapted to the extreme hypoxic environment. High aldosterone levels are believed to be involved in HA disorders, we, therefore, envisaged role of CYP11B2 gene variants in HA adaptation and therefore investigated the -344T/C, intron-2 conversion (Iw/Ic), K173R, and A5160C polymorphisms. In addition, polymorphisms in AGT, AT1R, ATP1A1, ADRB2, and GSTP1 genes were also investigated. The study comprised of 662 subjects, comprising of 426 Himalayan highlanders (HLs) and 236 lowlanders (LLs). The -344T/C and K173R polymorphisms were found to be in complete linkage disequilibrium. The wild-type allele -344T and combination of wild-type homozygous genotypes between -344T/C, Iw/Ic, and A5160C polymorphisms, containing all the six wild-type alleles were over-represented in the HLs (p < 0.0001, and p = 0.008, respectively). The wild-type haplotypes -344T-Iw, -344T-5160A, and -344T-Iw-5160A also showed over-representation in the HLs (p < 0.0001). Furthermore, greater the number of wild-type alleles, lower was the ARR (p < 0.05). The genotype distribution in remaining genes did not differ. To conclude, the over-representation of wild-type -344T allele, genotype combinations and haplotypes of CYP11B2, and their correlation with lower aldosterone levels associate with HA adaptation in the HLs. Such an allelic presentation in sojourners may help them cope with adverse HA environment. 相似文献
60.