全文获取类型
收费全文 | 804篇 |
免费 | 72篇 |
国内免费 | 32篇 |
出版年
2023年 | 17篇 |
2022年 | 14篇 |
2021年 | 15篇 |
2020年 | 15篇 |
2019年 | 18篇 |
2018年 | 16篇 |
2017年 | 17篇 |
2016年 | 24篇 |
2015年 | 27篇 |
2014年 | 33篇 |
2013年 | 40篇 |
2012年 | 19篇 |
2011年 | 51篇 |
2010年 | 31篇 |
2009年 | 35篇 |
2008年 | 60篇 |
2007年 | 70篇 |
2006年 | 41篇 |
2005年 | 41篇 |
2004年 | 31篇 |
2003年 | 35篇 |
2002年 | 28篇 |
2001年 | 22篇 |
2000年 | 16篇 |
1999年 | 18篇 |
1998年 | 22篇 |
1997年 | 19篇 |
1996年 | 16篇 |
1995年 | 6篇 |
1994年 | 8篇 |
1993年 | 11篇 |
1992年 | 9篇 |
1991年 | 10篇 |
1990年 | 7篇 |
1989年 | 9篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 7篇 |
1985年 | 7篇 |
1984年 | 7篇 |
1983年 | 8篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1971年 | 2篇 |
排序方式: 共有908条查询结果,搜索用时 31 毫秒
61.
Bin Xue Roland L. Dunbrack Robert W. Williams A. Keith Dunker Vladimir N. Uversky 《Biochimica et Biophysica Acta - Proteins and Proteomics》2010,1804(4):996-1010
Protein intrinsic disorder is becoming increasingly recognized in proteomics research. While lacking structure, many regions of disorder have been associated with biological function. There are many different experimental methods for characterizing intrinsically disordered proteins and regions; nevertheless, the prediction of intrinsic disorder from amino acid sequence remains a useful strategy especially for many large-scale proteomic investigations. Here we introduced a consensus artificial neural network (ANN) prediction method, which was developed by combining the outputs of several individual disorder predictors. By eight-fold cross-validation, this meta-predictor, called PONDR-FIT, was found to improve the prediction accuracy over a range of 3 to 20% with an average of 11% compared to the single predictors, depending on the datasets being used. Analysis of the errors shows that the worst accuracy still occurs for short disordered regions with less than ten residues, as well as for the residues close to order/disorder boundaries. Increased understanding of the underlying mechanism by which such meta-predictors give improved predictions will likely promote the further development of protein disorder predictors. Access to PONDR-FIT is available at www.disprot.org. 相似文献
62.
In this work we have investigated the effect of a pathogenic mitochondrial DNA mutation found in human colon cells, at a functional-molecular level. The mutation results in the amino-acid substitution Tyr19His in subunit I of the human CytcO and it is associated with respiratory deficiency. It was introduced into Rhodobacter sphaeroides, which carries a cytochrome c oxidase (cytochrome aa3) that serves as a model of the mitochondrial counterpart. The residue is situated in the middle of a pathway that is used to transfer substrate protons as well as protons that are pumped across the membrane. The Tyr33His (equivalent residue in the bacterial CytcO) structural variant of the enzyme was purified and its function was investigated. The results show that in the structurally altered CytcO the activity decreased due to slowed proton transfer; proton transfer from an internal proton donor, the highly-conserved Glu286, to the catalytic site was slowed by a factor of ∼ 5, while reprotonation of the Glu from solution was slowed by a factor of ∼ 40. In addition, in the structural variant proton pumping was completely impaired. These results are explained in terms of introduction of a barrier for proton transfer through the D pathway and changes in the coordination of water molecules surrounding the Glu286 residue. The study offers an explanation, at the molecular level, to the link between a specific amino-acid substitution and a pathogenic phenotype identified in human colon cells. 相似文献
63.
Water dynamics clue to key residues in protein folding 总被引:1,自引:0,他引:1
Meng Gao Xin-Qiu Yao Zhen-Su She 《Biochemical and biophysical research communications》2010,392(1):95-10887
A computational method independent of experimental protein structure information is proposed to recognize key residues in protein folding, from the study of hydration water dynamics. Based on all-atom molecular dynamics simulation, two key residues are recognized with distinct water dynamical behavior in a folding process of the Trp-cage protein. The identified key residues are shown to play an essential role in both 3D structure and hydrophobic-induced collapse. With observations on hydration water dynamics around key residues, a dynamical pathway of folding can be interpreted. 相似文献
64.
Rosario A. Muñoz-Clares Ángel G. Díaz-Sánchez Lilian González-Segura Carmina Montiel 《Archives of biochemistry and biophysics》2010,493(1):71-452
The betaine aldehyde dehydrogenases (BADH; EC 1.2.1.8) are so-called because they catalyze the irreversible NAD(P)+-dependent oxidation of betaine aldehyde to glycine betaine, which may function as (i) a very efficient osmoprotectant accumulated by both prokaryotic and eukaryotic organisms to cope with osmotic stress, (ii) a metabolic intermediate in the catabolism of choline in some bacteria such as the pathogen Pseudomonas aeruginosa, or (iii) a methyl donor for methionine synthesis. BADH enzymes can also use as substrates aminoaldehydes and other quaternary ammonium and tertiary sulfonium compounds, thereby participating in polyamine catabolism and in the synthesis of γ-aminobutyrate, carnitine, and 3-dimethylsulfoniopropionate. This review deals with what is known about the kinetics and structural properties of these enzymes, stressing those properties that have only been found in them and not in other aldehyde dehydrogenases, and discussing their mechanistic and regulatory implications. 相似文献
65.
Abstract: The impacts of four pesticides used for control of citrus thrips, Scirtothrips citri (Moulton), were evaluated in both field and laboratory populations of a predaceous mite, Euseius tularensis Congdon. Abamectin and chlorfenapyr had the least impact of pesticides evaluated on a field population of E. tularensis and predaceous mite levels mirrored those observed in the untreated control but at a slightly depressed level. Spinosad reduced predaceous mites somewhat but they recovered to 50% of the level in the untreated control by the end of the trial. Mite populations were low throughout the trial in plots treated with cyfluthrin. As an overall summary statistic, cumulative predator mite-days ranged from 73.6% of the level observed in the untreated control with abamectin to 67.1% with chlorfenapyr, 36.8% with spinosad and 11.7% with cyfluthrin. Three additional field trials confirmed abamectin's minimal impact. In laboratory studies of adult female mite mortality on field-weathered, pesticide-treated leaves, cyfluthrin caused high mortality on day 1 after treatment and all mites that were not killed were driven off leaf discs until day 21. When mites were placed on leaf discs 1 day after treatment with abamectin, spinosad, or chlorfenapyr, 67.5% of the mites died on chlorfenapyr discs. By 7 days after treatment, no material but cyfluthrin showed a significant impact. Implications to citrus integrated pest management are discussed. 相似文献
66.
67.
The SR protein kinase in yeast, Sky1p, phosphorylates yeast SR-like protein, Npl3p, at a single serine residue located at its C terminus. We report here the X-ray crystal structure of Sky1p bound to a substrate peptide and ADP. Surprisingly, an Npl3p-derived substrate peptide occupies a groove 20 A away from the kinase active site. In vitro studies support the substrate-docking role of this groove. Mutagenesis and binding studies reveal that multiple degenerate short peptide motifs located within the RGG domain of Npl3p serve as the substrate docking motifs. However, a single docking motif is sufficient for its stable interaction with the kinase. Methylation of the docking motifs abolishes kinase binding and phosphorylation of Npl3p. Remarkably, removal of the docking groove in the kinase or the docking motifs of the substrate does not reduce the overall catalytic efficiency of the phosphorylation reaction in any significant manner. We suggest that docking interaction between Sky1p and Npl3p is essential for substrate recruitment and binding specificity. 相似文献
68.
The function of the src-homology 3 (SH3) domain in class II myosins, a distinct beta-barrel structure, remains unknown. Here, we provide evidence, using electron cryomicroscopy, in conjunction with light-scattering, fluorescence and kinetic analyses, that the SH3 domain facilitates the binding of the N-terminal extension of the essential light chain isoform (ELC-1) to actin. The 41 residue extension contains four conserved lysine residues followed by a repeating sequence of seven Pro/Ala residues. It is widely believed that the highly charged region interacts with actin, while the Pro/Ala-rich sequence forms a rigid tether that bridges the approximately 9 nm distance between the myosin lever arm and the thin filament. In order to localize the N terminus of ELC in the actomyosin complex, an engineered Cys was reacted with undecagold-maleimide, and the labeled ELC was exchanged into myosin subfragment-1 (S1). Electron cryomicroscopy of S1-bound actin filaments, together with computer-based docking of the skeletal S1 crystal structure into 3D reconstructions, showed a well-defined peak for the gold cluster near the SH3 domain. Given that SH3 domains are known to bind proline-rich ligands, we suggest that the N-terminal extension of ELC interacts with actin and modulates myosin kinetics by binding to the SH3 domain during the ATPase cycle. 相似文献
69.
Hede MS Petersen RL Frøhlich RF Krüger D Andersen FF Andersen AH Knudsen BR 《Journal of molecular biology》2007,365(4):1076-1092
Prompted by the close relationship between tyrosine recombinases and type IB topoisomerases we have investigated the ability of human topoisomerase I to resolve the typical intermediate of recombinase catalysis, the Holliday junction. We demonstrate that human topoisomerase I catalyzes unidirectional resolution of a synthetic Holliday junction substrate containing two preferred cleavage sites surrounded by DNA sequences supporting branch migration. Deleting part of the N-terminal domain (amino acid residues 1-202) did not affect topoisomerase I resolution activity, whereas a topoisomerase I variant lacking both the N-terminal domain and amino acid residues 660-688 of the linker domain was unable to resolve the Holliday junction substrate. The inability of the double deleted variant to mediate resolution correlated with the inability of this enzyme to introduce concomitant cleavage at the two preferred cleavage sites in a single Holliday junction substrate, which is a prerequisite for resolution. As determined by the gel electrophoretic mobility of native enzyme or enzyme crosslinked by disulfide bridging, the double deleted mutant existed almost entirely in a dimeric form. The impairment of this enzyme in performing double cleavages on the Holliday junction substrate may be explained by only one cleavage competent active site being formed at a time within the dimer. The assembly of only one active site within dimers is a well-known characteristic of the tyrosine recombinases. Hence, the obtained results may suggest a recombinase-like active site assembly of the double deleted topoisomerase I variant. Taken together the presented results consolidate the relationship between type IB topoisomerases and tyrosine recombinases. 相似文献
70.