全文获取类型
收费全文 | 7146篇 |
免费 | 873篇 |
国内免费 | 506篇 |
专业分类
8525篇 |
出版年
2024年 | 22篇 |
2023年 | 177篇 |
2022年 | 189篇 |
2021年 | 258篇 |
2020年 | 340篇 |
2019年 | 436篇 |
2018年 | 393篇 |
2017年 | 402篇 |
2016年 | 369篇 |
2015年 | 340篇 |
2014年 | 390篇 |
2013年 | 651篇 |
2012年 | 254篇 |
2011年 | 388篇 |
2010年 | 290篇 |
2009年 | 430篇 |
2008年 | 437篇 |
2007年 | 377篇 |
2006年 | 355篇 |
2005年 | 263篇 |
2004年 | 291篇 |
2003年 | 203篇 |
2002年 | 167篇 |
2001年 | 157篇 |
2000年 | 121篇 |
1999年 | 112篇 |
1998年 | 124篇 |
1997年 | 88篇 |
1996年 | 82篇 |
1995年 | 79篇 |
1994年 | 63篇 |
1993年 | 73篇 |
1992年 | 67篇 |
1991年 | 33篇 |
1990年 | 24篇 |
1989年 | 11篇 |
1988年 | 11篇 |
1987年 | 8篇 |
1986年 | 13篇 |
1985年 | 5篇 |
1984年 | 7篇 |
1983年 | 5篇 |
1982年 | 7篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1976年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有8525条查询结果,搜索用时 0 毫秒
191.
Hugo M. Martinez Jacob V. Maizel Jr Bruce A. Shapiro 《Journal of biomolecular structure & dynamics》2013,31(6):669-683
Abstract Using primary and secondary structure information of an RNA molecule, the program RNA2D3D automatically and rapidly produces a first-order approximation of a 3-dimensional conformation consistent with this information. Applicable to structures of arbitrary branching complexity and pseudoknot content, it features efficient interactive graphical editing for the removal of any overlaps introduced by the initial generating procedure and for making conformational changes favorable to targeted features and subsequent refinement. With emphasis on fast exploration of alternative 3D conformations, one may interactively add or delete base-pairs, adjacent stems can be coaxially stacked or unstacked, single strands can be shaped to accommodate special constraints, and arbitrary subsets can be defined and manipulated as rigid bodies. Compaction, whereby base stacking within stems is optimally extended into connecting single strands, is also available as a means of strategically making the structures more compact and revealing folding motifs. Subsequent refinement of the first-order approximation, of modifications, and for the imposing of tertiary constraints is assisted with standard energy refinement techniques. Previously determined coordinates for any part of the molecule are readily incorporated, and any part of the modeled structure can be output as a PDB or XYZ file. Illustrative applications in the areas of ribozymes, viral kissing loops, viral internal ribosome entry sites, and nanobiology are presented. 相似文献
192.
Hong-Lian Li Chang-Jie Zheng Wen-Yan Jin Wen-Shan Liu 《Journal of biomolecular structure & dynamics》2013,31(14):3856-3868
Noonan syndrome (NS) is a common autosomal dominant congenital disorder which could cause the congenital cardiopathy and cancer predisposition. Previous studies reported that the knock-in mouse models of the mutant D61G of SHP2 exhibited the major features of NS, which demonstrated that the mutation D61G of SHP2 could cause NS. To explore the effect of D61G mutation on SHP2 and explain the high activity of the mutant, molecular dynamic simulations were performed on wild type (WT) of SHP2 and the mutated SHP2-D61G, respectively. The principal component analysis and dynamic cross-correlation mapping, associated with secondary structure, showed that the D61G mutation affected the motions of two regions (residues Asn 58-Thr 59 and Val 460-His 462) in SHP2 from β to turn. Moreover, the residue interaction networks analysis, the hydrogen bond occupancy analysis and the binding free energies were calculated to gain detailed insight into the influence of the mutant D61G on the two regions, revealing that the major differences between SHP2-WT and SHP2-D61G were the different interactions between Gly 61 and Gly 462, Gly 61 and Ala 461, Gln 506 and Ile 463, Gly 61 and Asn 58, Ile 463 and Thr 466, Gly 462 and Cys 459. Consequently, our findings here may provide knowledge to understand the increased activity of SHP2 caused by the mutant D61G. 相似文献
193.
Sinosh Skariyachan Nisha Jayaprakash Navya Bharadwaj 《Journal of biomolecular structure & dynamics》2013,31(9):1379-1395
In our recent studies on prevalence of multidrug resistant pathogens in Byramangala reservoir, Karnataka, India, we identified Salmonella typhi, Staphylococcus aureus, and Vibrio cholerae which had acquired multiple drug resistance (MDR) and emerged as superbugs. Hence, there is a pressing demand to identify alternative therapeutic remedies. Our study focused on the screening of herbal leads by structure-based virtual screening. The virulent gene products of these pathogens towards Kanamycin(aph), Trimethoprim(dfrA1), Methicillin (mecI), and Vancomycin (vanH) were identified as the probable drug targets and their 3D structures were predicted by homology modeling. The predicted models showed good stereochemical validity. By extensive literature survey, we selected 58 phytoligands and their drug likeliness and pharmacokinetic properties were computationally predicted. The inhibitory properties of these ligands against drug targets were studied by molecular docking. Our studies revealed that Baicalein from S. baicalensis (baikal skullcap) and Luteolin from Taraxacum officinale (dandelion) were identified as potential inhibitors against aph of S. typhi. Resveratrol from Vitis vinifera (grape vine) and Wogonin from S. baicalensis were identified as potential inhibitors against dfrA1 of S. typhi. Herniarin from Herniaria glabra (rupture worts) and Pyrocide from Daucus carota (Carrot) were identified as the best leads against dfrA1 of V. cholerae. Taraxacin of T. officinale (weber) and Luteolin were identified as potential inhibitors against Mec1. Apigenin from Coffee arabica (coffee) and Luteolin were identified as the best leads against vanH of S. aureus. Our findings pave crucial insights for exploring alternative therapeutics against MDR pathogens. 相似文献
194.
本文研究了华北棉花-玉米农田景观格局中龟纹瓢虫Propylaea japonica(Thunberg)和异色瓢虫Harmonia axyridis(Pallas)种群动态,发现农田景观格局中作物类型(棉花与玉米)对两种瓢虫种群密度动态有显著的影响,两种天敌瓢虫都趋向在玉米斑块上栖息。两种瓢虫在棉花斑块上呈现出时间分化,其中龟纹瓢虫在棉花种植的前中期种群密度较大,后期较少;而异色瓢虫在棉花前中期种群密度较少,后期较多,表明农田景观中种植玉米有利于增强瓢虫对棉花害虫的控制作用。进一步的研究表明,农田景观系统中玉米斑块所占的面积比对龟纹瓢虫和异色瓢虫种群密度均产生显著影响。这说明在农田景观系统中开展区域性生态调控的时候,需要考虑到各类斑块组合的面积比例,从而有利于增强多种天敌昆虫的协调控害作用。 相似文献
195.
《Chronobiology international》2013,30(5):1124-1134
Using structural equation modeling, it can be shown that long weekly working hours and work on weekends, nights, and in shifts have detrimental effects on psychovegetative health. Employees' reported subjective work-life balance also decreases with increasing number of hours worked/week, days worked on weekends, or at nights, and with working shifts. A decrease in work-life balance in turn increases the risk of psychovegetative impairments (PVIs). Thus, long and unusual working hours increase the risk of psychovegetative health impairments both directly and indirectly, moderated by the subjective work-life balance. In fact, the indirect effects of working time on PVIs via the work-life balance seem to be stronger than the direct effects. Results of a cross-validation study of four independent and representative samples from Germany and the European Union (N?>?50,000) indicate high structural stability of these results and thus an increased validity and range for generalization. (Author correspondence: anna. wirtz@gawo-ev. de) 相似文献
196.
《Chronobiology international》2013,30(2):191-192
Most variables of interest in laboratory medicine show predictable changes with several frequencies in the span of time investigated. The waveform of such nonsinusoidal rhythms can be well described by the use of multiple components rhythmometry, a method that allows fitting a linear model with several cosine functions. The method, originally described for analysis of longitudinal time series, is here extended to allow analysis of hybrid data (time series sampled from a group of subjects, each represented by an individual series). Given k individual series, we can fit the same linear model with m different frequencies (harmonics or not from one fundamental period) to each series. This fit will provide estimations for 2m + 1 parameters, namely, the amplitude and acrophase of each component, as well as the rhythm-adjusted mean. Assuming that the set of parameters obtained for each individual is a random sample from a multivariate normal population, the corresponding population parameter estimates can be based on the means of estimates obtained from individuals in the sample. Their confidence intervals depend on the variability among individual parameter estimates. The vari-ance-covariance matrix can then be estimated on the basis of the sample covariances. Confidence intervals for the rhythm-adjusted mean, as well as for the amplitude-acrophase pair, of each component can then be computed using the estimated covariance matrix. The p-values for testing the zero-amplitude assumption for each component, as well as for the global model, can finally be derived using those confidence intervals and the t and F distributions. The method, validated by a simulation study and illustrated by an example of modeling the circadian variation of heart rate, represents a new step in the development of statistical procedures in chronobiology. 相似文献
197.
Abstract Lipid bilayer plays a crucial role in folding of membrane peptides and their stabilization in the membrane-bound state. Correct treatment of the media effects is thus essential for realistic simulations of peptides in bilayers. Previously (Volynsky et al., 1999), we proposed an efficient solvation model which mimics heterogeneous membrane-water system. The model is based on combined employment of atomic solvation parameters for water and hydrocarbon, which approximate hydrated headgroups and acyl chains of lipids, respectively. In this study, the model is employed in non-restrained Monte Carlo simulations of several peptides: totally apolar 20-residue poly-L-Leu, hydrophobic peptide with polar edges, and strongly amphiphilic pep-tide. The principal goals are: to explore energy landscape of these peptides in membrane; to characterize the structures of low-energy states and their orientations with respect to the bilayer. Simulations were performed starting from different structures (unordered or helical) and orientations. It was found that the membrane environment significantly promotes an α-helical conformation for all the peptides, while their energetically favourable orientations are quite different. Thus, poly-Leu was immobilized inside the membrane, the hydrophobic peptide with polar termini adapted transbilayer orientation, whereas the amphiphilic peptide stayed on the lipid-water interface in peripherial orientation. Energy barriers between different states were characterized. The computational results were compared with the experimental structural data. 相似文献
198.
199.
Ivan Lule Pieter-Jan D’Huys Lieve Van Mellaert Jozef Anné Kristel Bernaerts Jan Van Impe 《Mathematical biosciences》2013
The metabolic impact exerted on a microorganism due to heterologous protein production is still poorly understood in Streptomyces lividans. In this present paper, based on exometabolomic data, a proposed genome-scale metabolic network model is used to assess this metabolic impact in S. lividans. Constraint-based modeling results obtained in this work revealed that the metabolic impact due to heterologous protein production is widely distributed in the genome of S. lividans, causing both slow substrate assimilation and a shift in active pathways. Exchange fluxes that are critical for model performance have been identified for metabolites of mouse tumor necrosis factor, histidine, valine and lysine, as well as biomass. Our results unravel the interaction of heterologous protein production with intracellular metabolism of S. lividans, thus, a possible basis for further studies in relieving the metabolic burden via metabolic or bioprocess engineering. 相似文献
200.
Ana C. Santos Joana Cunha F. Veiga A. Cordeiro-da-Silva Antonio J. Ribeiro 《Carbohydrate polymers》2013
Alginate-dextran sulfate (ADS) microgel has been used to protect insulin from gastrointestinal attack and as a carrier to promote insulin permeation through intestinal epithelium. The throughput of ADS submicron particles generation by emulsification/internal gelation is limited by its wide size distribution. 相似文献