全文获取类型
收费全文 | 2820篇 |
免费 | 340篇 |
国内免费 | 260篇 |
专业分类
3420篇 |
出版年
2024年 | 18篇 |
2023年 | 112篇 |
2022年 | 96篇 |
2021年 | 96篇 |
2020年 | 130篇 |
2019年 | 138篇 |
2018年 | 98篇 |
2017年 | 80篇 |
2016年 | 104篇 |
2015年 | 111篇 |
2014年 | 136篇 |
2013年 | 205篇 |
2012年 | 128篇 |
2011年 | 119篇 |
2010年 | 103篇 |
2009年 | 130篇 |
2008年 | 183篇 |
2007年 | 163篇 |
2006年 | 170篇 |
2005年 | 155篇 |
2004年 | 152篇 |
2003年 | 130篇 |
2002年 | 99篇 |
2001年 | 71篇 |
2000年 | 45篇 |
1999年 | 44篇 |
1998年 | 66篇 |
1997年 | 51篇 |
1996年 | 43篇 |
1995年 | 58篇 |
1994年 | 36篇 |
1993年 | 26篇 |
1992年 | 18篇 |
1991年 | 19篇 |
1990年 | 5篇 |
1989年 | 11篇 |
1988年 | 8篇 |
1987年 | 7篇 |
1986年 | 3篇 |
1985年 | 5篇 |
1984年 | 12篇 |
1983年 | 7篇 |
1982年 | 8篇 |
1981年 | 5篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1977年 | 2篇 |
1973年 | 4篇 |
1972年 | 2篇 |
1971年 | 2篇 |
排序方式: 共有3420条查询结果,搜索用时 0 毫秒
1.
D. Allen Clabo Jr. Hamilton D. Dickson Toby L. Nelson 《Journal of molecular modeling》2000,6(2):341-348
Semiempirical and ab initio theoretical methods have been used to investigate molecular structures of the chalcogen-substituted carboxylic acid isomers RC(=O)XH (chalcogenol acid) and RC(=X)OH (chalcogenon acid). A recent experimental report suggests that the chalcogenon isomers, although less stable at room temperature, predominate at low temperature in polar solvents and that there is only a small barrier to isomerization between the isomers. Theoretical calculations have been used to locate minimum energy structures of chalcogen-substituted carboxylic acid isomers and to calculate energy differences between pairs of isomers. Carboxylic acids are well known to dimerize, especially in the gas phase and in non-polar solvents. We have, therefore, also calculated energies of dimerization of the chalcogen-substituted acids by optimizing the geometries of the symmetric dimers. We note that the PM3 level of theory is only qualitatively correct for sulfur- and selenium-containing species but fails even qualitatively for the tellurium-containing compounds. Ab initio results confirm the experimental observations and provide good estimates of both isomerization and dimerization energies. We conclude that for many functional groups with tautomers RC(=X)YH and RC(=Y)XH, the more acidic tautomer is the one with the acid proton on the smaller, more electronegative atom, although in many cases this may not be the more stable tautomer.Electronic Supplementary Material available. 相似文献
2.
3.
R F Sturrock 《International journal for parasitology》1973,3(2):165-174
Growth curves, calculated for field populations of B. glabrata, were not materially affected by habitat, altitude or season. A mean growth curve was therefore used to estimate the age-frequency distribution of snails in successive field samples. These data permitted the construction of ecological life tables and the estimation of r, the intrinsic rate of natural increase (or decrease) of the different populations. The calculated values of r were inserted in a simple model of unlimited population growth but the resultant curves poorly represented the observed data. A model for unlimited growth was more satisfactory for pond and marsh populations but, apparently, immigration made it less satisfactory for stream and banana drain populations. Nevertheless, r may still be of value in predicting repopulation rates in certain habitats after a mollusciciding which does not kill the entire snail population. 相似文献
4.
《Journal of biological dynamics》2013,7(4):357-385
A system of ordinary differential equations is formulated to describe the pathogenesis of HIV infection, wherein certain features that have been shown to be important by recent experimental research are incorporated in the model. These include the role of CD4+memory cells that serve as a major reservoir of latently infected cells, a critical role for T-helper cells in the generation of CD8 memory cells capable of efficient recall response, and stimulation by antigens other than HIV. A stability analysis illustrates the capability of this model in admitting multiple locally asymptotically stable (locally a.s.) off-treatment equilibria. We show that this more biologically detailed model can exhibit the phenomenon of transient viremia experienced by some patients on therapy with viral load levels suppressed below the detection limit. We also show that the loss of CD4+T-cell help in the generation of CD8+memory cells leads to larger peak values for the viral load during transient viremia. Censored clinical data is used to obtain parameter estimates. We demonstrate that using a reduced set of 16 free parameters, obtained by fixing some parameters at their population averages, the model provides reasonable fits to the patient data and, moreover, that it exhibits good predictive capability. We further show that parameter values obtained for most clinical patients do not admit multiple locally a.s off-treatment equilibria. This suggests that treatment to move from a high viral load equilibrium state to an equilibrium state with a lower (or zero) viral load is not possible for these patients. 相似文献
5.
A method is proposed for predicting the adjacency order in which strands pack in a -sheet in a protein, on the basis of its amino acid sequence alone. The method is based on the construction of a predicted contact map for the protein, in which the probability that various residue pairs are close to each other is computed from statistically determined average distances of residue pairs in globular proteins of known structure. Compact regions, i.e., portions of the sequence with many interresidue contacts, are determined on the map by using an objective search procedure. The proximity of strands in a -sheet is predicted from the density of contacts in compact regions associated with each pair of strands. The most probable -sheet structures are those with the highest density of contacts. The method has been tested by computing the probable strand arrangements in a five-strand -sheet in five proteins or protein domains, containing 62–138 residues. Of the theoretically possible 60 strand arrangements, the method selects two to eight arrangements as most probable; i.e., it leads to a large reduction in the number of possibilities. The native strand arrangement is among those predicted for three of the five proteins. For the other two, it would be included in the prediction by a slight relaxation of the cutoff criteria used to analyze the density of contacts. 相似文献
6.
Detection of native-like models for amino acid sequences of unknown three-dimensional structure in a data base of known protein conformations. 总被引:13,自引:0,他引:13
We present an approach which can be used to identify native-like folds in a data base of protein conformations in the absence of any sequence homology to proteins in the data base. The method is based on a knowledge-based force field derived from a set of known protein conformations. A given sequence is mounted on all conformations in the data base and the associated energies are calculated. Using several conformations and sequences from the globin family we show that the native conformation is identified correctly. In fact the resolution of the force field is high enough to discriminate between a native fold and several closely related conformations. We then apply the procedure to several globins of known sequence but unknown three dimensional structure. The homology of these sequences to globins of known structures in the data base ranges from 49 to 17%. With one exception we find that for all globin sequences one of the known globin folds is identified as the most favorable conformation. These results are obtained using a force field derived from a data base devoid of globins of known structure. We briefly discuss useful applications in protein structural research and future development of our approach. 相似文献
7.
A directed conformational search algorithm using the program CONGEN (ref. 3), which samples backbone conformers, is described. The search technique uses information from the partially built structures to direct the search process and is tested on the problem of generating a full set of backbone Cartesian coordinates given only alpha-carbon coordinates. The method has been tested on six proteins of known structure, varying in size and classification, and was able to generate the original backbone coordinates with RMSs ranging from 0.30-0.87A for the alpha-carbons and 0.5-0.99A RMSs for the backbone atoms. Cis peptide linkages were also correctly identified. The procedure was also applied to two proteins available with only alpha-carbon coordinates in the Brookhaven Protein Data Bank; thioredoxin (SRX) and triacylglycerol acylhydrolase (TGL). All-atom models are proposed for the backbone of both these proteins. In addition, the technique was applied to randomized coordinates of flavodoxin to assess the effects of irregularities in the data on the final RMS. This study represents the first time a deterministic conformational search was used on such a large scale. 相似文献
8.
Thérèse E. Malliavin Marc A. Delsuc Jean Y. Lallemand 《Journal of biomolecular NMR》1992,2(4):349-360
Summary The structural determination of biological molecules in solution by NMR relies on the determination of a set of interatomic distances obtained by measurement of intramolecular nuclear Overhauser effects (NOE). It is shown in this paper that it is possible to obtain the accurate relaxation rate (and hence the interatomic distance) from the direct measurement of a single NOE signal. The precise analysis of a NOESY peak evolution with respect to the mixing time allows the evaluation of the relaxation parameters for the pair of spins under consideration. This is done without any assumption on the relaxation of unmeasured spins, or on the movement of the molecule. The theoretical basis of this method is presented. In order to evaluate the proposed method, a simulated case on the protein BPTI is studied, which shows that the method performs very well even in the case of noisy data sets. 相似文献
9.
Environment-specific amino acid substitution tables: tertiary templates and prediction of protein folds. 总被引:4,自引:0,他引:4
下载免费PDF全文
![点击此处可从《Protein science : a publication of the Protein Society》网站下载免费的PDF全文](/ch/ext_images/free.gif)
J Overington D Donnelly M S Johnson A Sali T L Blundell 《Protein science : a publication of the Protein Society》1992,1(2):216-226
The local environment of an amino acid in a folded protein determines the acceptability of mutations at that position. In order to characterize and quantify these structural constraints, we have made a comparative analysis of families of homologous proteins. Residues in each structure are classified according to amino acid type, secondary structure, accessibility of the side chain, and existence of hydrogen bonds from the side chains. Analysis of the pattern of observed substitutions as a function of local environment shows that there are distinct patterns, especially for buried polar residues. The substitution data tables are available on diskette with Protein Science. Given the fold of a protein, one is able to predict sequences compatible with the fold (profiles or templates) and potentially to discriminate between a correctly folded and misfolded protein. Conversely, analysis of residue variation across a family of aligned sequences in terms of substitution profiles can allow prediction of secondary structure or tertiary environment. 相似文献
10.
Ribonuclease Ms from Aspergillus saitoi is a small acidic protein (11 714 Da) containing 106 amino acids of known sequence. Unlike other enzymes belonging to the RNase T1 family this ribonuclease is base-unspecific. Using interactive computer graphics and energy minimisation we predicted the structure of RNase Ms on the basis of sequence homology to RNase T1 of known structure. In this report the predicted structure of this protein is presented and characterised. 相似文献