全文获取类型
收费全文 | 17100篇 |
免费 | 1398篇 |
国内免费 | 1727篇 |
出版年
2024年 | 29篇 |
2023年 | 247篇 |
2022年 | 459篇 |
2021年 | 1017篇 |
2020年 | 726篇 |
2019年 | 871篇 |
2018年 | 787篇 |
2017年 | 620篇 |
2016年 | 828篇 |
2015年 | 1141篇 |
2014年 | 1391篇 |
2013年 | 1397篇 |
2012年 | 1688篇 |
2011年 | 1512篇 |
2010年 | 933篇 |
2009年 | 800篇 |
2008年 | 839篇 |
2007年 | 797篇 |
2006年 | 654篇 |
2005年 | 545篇 |
2004年 | 398篇 |
2003年 | 400篇 |
2002年 | 338篇 |
2001年 | 269篇 |
2000年 | 217篇 |
1999年 | 228篇 |
1998年 | 155篇 |
1997年 | 121篇 |
1996年 | 133篇 |
1995年 | 102篇 |
1994年 | 90篇 |
1993年 | 57篇 |
1992年 | 76篇 |
1991年 | 64篇 |
1990年 | 51篇 |
1989年 | 59篇 |
1988年 | 30篇 |
1987年 | 39篇 |
1986年 | 30篇 |
1985年 | 24篇 |
1984年 | 16篇 |
1983年 | 17篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 3篇 |
1973年 | 2篇 |
1970年 | 2篇 |
1968年 | 2篇 |
1953年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Predictive pharmacophore models were developed for a large series of I(Kr) potassium channel blockers as class III antiarrhythmic agents using HypoGen in Catalyst software. The pharmacophore hypotheses were generated using a training set consisting of 34 compounds carefully selected from documents. Their biological data, expressed as IC(50), spanned from 1.5 nM to 2.8 mM with 7 orders difference. The most predictive hypothesis (Hypo1), consisting of four features (one positive ionizable feature, two aromatic rings and one hydrophobic group), had a best correlation coefficient of 0.825, a lowest rms deviation of 1.612, and a highest cost difference (null cost-total cost) of 77.552, which represents a true correlation and a good predictivity. The hypothesis Hypo1 was then validated by a test set consisting of 21 compounds and by a cross-validation of 95% confidence level with randomizing the data using CatScramble program. Accordingly, our model has strong predictivity to identify structural diverse I(Kr) potassium channel blockers with desired biological activity by virtual screening 相似文献
992.
Qing G Ma LC Khorchid A Swapna GV Mal TK Takayama MM Xia B Phadtare S Ke H Acton T Montelione GT Ikura M Inouye M 《Nature biotechnology》2004,22(7):877-882
Overexpression of proteins in Escherichia coli at low temperature improves their solubility and stability. Here, we apply the unique features of the cspA gene to develop a series of expression vectors, termed pCold vectors, that drive the high expression of cloned genes upon induction by cold-shock. Several proteins were produced with very high yields, including E. coli EnvZ ATP-binding domain (EnvZ-B) and Xenopus laevis calmodulin (CaM). The pCold vector system can also be used to selectively enrich target proteins with isotopes to study their properties in cell lysates using NMR spectroscopy. We have cloned 38 genes from a range of prokaryotic and eukaryotic organisms into both pCold and pET14 (ref. 3) systems, and found that pCold vectors are highly complementary to the widely used pET vectors. 相似文献
993.
Datta S Satten GA Benos DJ Xia J Heslin MJ Datta S 《Bioinformatics (Oxford, England)》2004,20(2):235-242
MOTIVATION: Detection of differentially expressed genes is one of the major goals of microarray experiments. Pairwise comparison for each gene is not appropriate without controlling the overall (experimentwise) type 1 error rate. Dudoit et al. have advocated use of permutation-based step-down P-value adjustments to correct the observed significance levels for the individual (i.e. for each gene) two sample t-tests. RESULTS: In this paper, we consider an ANOVA formulation of the gene expression levels corresponding to multiple tissue types. We provide resampling-based step-down adjustments to correct the observed significance levels for the individual ANOVA t-tests for each gene and for each pair of tissue type comparisons. More importantly, we introduce a novel empirical Bayes adjustment to the t-test statistics that can be incorporated into the step-down procedure. Using simulated data, we show that the empirical Bayes adjustment improved the sensitivity of detecting differentially expressed genes up to 16%, while maintaining a high level of specificity. This adjustment also reduces the false non-discovery rate to some degree at the cost of a modest increase in the false discovery rate. We illustrate our approach using a human colon cancer dataset consisting of oligonucleotide arrays of normal, adenoma and carcinoma cells. The number of genes with differential expression level declared statistically significant was about 50 when comparing normal to adenoma cells and about five when comparing adenoma to carcinoma cells. This list includes genes previously known to be associated with colon cancer as well as some novel genes. AVAILABILITY: R code for the empirical Bayes adjustment and step-down P-value calculation via resampling are available from the supplementary web-site. Supplementary information: http://www.mathstat.gsu.edu/~matsnd/EB/supp.htm 相似文献
994.
Dhar P Meng TC Somani S Ye L Sairam A Chitre M Hao Z Sakharkar K 《Bioinformatics (Oxford, England)》2004,20(8):1319-1321
The intracellular environment of a cell hosts a wide variety of enzymatic reactions, diffusion events, molecular binding, polymerization and metabolic channeling. To transform these biological events into a computational framework, distinct modeling strategies are required. While currently no tool is capable of capturing all these events, progress is being made to create an integrated environment for the modeling community. To address this niche requirement, Cellware has been developed to offer a multi-algorithmic environment for modeling and simulating both deterministic and stochastic events in the cell. AVAILABILITY: The software is available for free and can be downloaded from http://www.bii.a-star.edu.sg/sbg/cellware 相似文献
995.
CFP10 discriminates between nonacetylated and acetylated ESAT-6 of Mycobacterium tuberculosis by differential interaction 总被引:2,自引:0,他引:2
Okkels LM Müller EC Schmid M Rosenkrands I Kaufmann SH Andersen P Jungblut PR 《Proteomics》2004,4(10):2954-2960
ESAT-6 (the 6 kDa early secreted antigenic target) protein species in short-term culture filtrate of Mycobacterium tuberculosis were separated in a 4-5 narrow range pI gradient two-dimensional gel electrophoresis (2-DE). Eight ESAT-6 protein species were analyzed in detail by peptide mass fingerprinting matrix-assisted laser desorption/ionization-mass spectrometry as well as by electrospray ionization-tandem mass spectrometry. An N-terminal Thr acetylation was identified in four species and a C-terminal truncation was identified in two species. In 2-DE blot overlay assays, the recombinant 10 kDa culture filtrate protein (CFP10) discriminated N-terminal acetylated and nonacetylated ESAT-6 by differential interaction, whereas removal of the C-terminal 11 residues of ESAT-6 had no effects thereon. This example shows that the access to the protein species level can be a prerequisite to understand regulation of protein-protein interaction. 相似文献
996.
Protection of mice with a divalent tuberculosis DNA vaccine encoding antigens Ag85B and MPT64 总被引:5,自引:0,他引:5
Tuberculosis (TB) remains to be a major challenge tothe public health in the world. It is estimated that, through-out the world, 15 individuals are affected by TB and 6 ofthem die from it every minute [1]. Drug resistance andcoinfection with HIV, which ut… 相似文献
997.
998.
Shijun?KangEmail author Rongcheng?Luo Wangjun?Liao Hubing?Wu Xuelin?Zhang Yuru?Meng 《World journal of surgical oncology》2004,2(1):30
Background
There is genuine need to develop interventional treatment options for management of lung tumors. Radiofrequency ablation (RFA) is one such alternative being promoted to treat lung tumors recently. Larger studies should help define RFA's further development. Furthermore fluorodeoxyglucose positron emission tomography (PET) has been reported to be an accurate indicator of treatment response in variety of tumors. This study focuses on the evaluating the feasibility of RFA and usefulness of PET scan in lung tumors after RFA procedure. 相似文献999.
Jiang XS Zhou H Zhang L Sheng QH Li SJ Li L Hao P Li YX Xia QC Wu JR Zeng R 《Molecular & cellular proteomics : MCP》2004,3(5):441-455
Four fractions from rat liver (a crude mitochondria (CM) and cytosol (C) fraction obtained with differential centrifugation, a purified mitochondrial (PM) fraction obtained with nycodenz density gradient centrifugation, and a total liver (TL) fraction) were analyzed with two-dimensional liquid chromatography tandem mass spectrometry analysis. A total of 564 rat proteins were identified and were bioinformatically annotated according to their physicochemical characteristics and functions. While most extreme alkaline ribosomal proteins were identified in the TL fraction, the C fraction mainly included neutral enzymes and the PM fraction enriched alkaline proteins and proteins with electron transfer activity or oxygen binding activity. Such characteristics were more apparent in proteins identified only in the TL, C, or PM fraction. The Swiss-Prot annotation and the bioinformatic prediction results proved that the C and PM fractions had enriched cytoplasmic or mitochondrial proteins, respectively. Combination usage of subcellular fractionation with two-dimensional liquid chromatography tandem mass spectrometry was proved to be a high-throughput, sensitive, and effective analytical approach for subcellular proteomics research. Using such a strategy, we have constructed the largest proteome database to date for rat liver (564 rat proteins) and its cytosol (222 rat proteins) and mitochondrial fractions (227 rat proteins). Moreover, the 352 proteins with Swiss-Prot subcellular location annotation in the 564 identified proteins were used as an actual subcellular proteome dataset to evaluate the widely used bioinformatics tools such as PSORT, TargetP, TMHMM, and GRAVY. 相似文献
1000.
Anti-AIDS agents. Part 56: Synthesis and anti-HIV activity of 7-thia-di-O-(-)-camphanoyl-(+)-cis-khellactone (7-thia-DCK) analogs 总被引:1,自引:0,他引:1
Chen Y Zhang Q Zhang B Xia P Xia Y Yang ZY Kilgore N Wild C Morris-Natschke SL Lee KH 《Bioorganic & medicinal chemistry》2004,12(24):67-6387
Two thia-DCK analogs (3a,b) were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. Compound 3a showed potent anti-HIV activity with an EC50 value of 0.14 μM and a therapeutic index of 1110. However, the corresponding 6-tert-butyl-substituted compound (3b) showed no suppression. The bioassay results indicated that thia-DCK analogs merit attention as potential HIV-1 inhibitors. 相似文献