全文获取类型
收费全文 | 3454篇 |
免费 | 283篇 |
国内免费 | 3篇 |
出版年
2023年 | 13篇 |
2022年 | 14篇 |
2021年 | 36篇 |
2020年 | 31篇 |
2019年 | 51篇 |
2018年 | 52篇 |
2017年 | 41篇 |
2016年 | 67篇 |
2015年 | 106篇 |
2014年 | 169篇 |
2013年 | 168篇 |
2012年 | 220篇 |
2011年 | 207篇 |
2010年 | 162篇 |
2009年 | 148篇 |
2008年 | 216篇 |
2007年 | 228篇 |
2006年 | 209篇 |
2005年 | 218篇 |
2004年 | 191篇 |
2003年 | 167篇 |
2002年 | 190篇 |
2001年 | 59篇 |
2000年 | 42篇 |
1999年 | 42篇 |
1998年 | 49篇 |
1997年 | 34篇 |
1996年 | 34篇 |
1995年 | 40篇 |
1994年 | 30篇 |
1993年 | 35篇 |
1992年 | 27篇 |
1991年 | 29篇 |
1990年 | 28篇 |
1989年 | 24篇 |
1988年 | 23篇 |
1987年 | 18篇 |
1986年 | 11篇 |
1985年 | 30篇 |
1984年 | 24篇 |
1983年 | 17篇 |
1982年 | 23篇 |
1981年 | 16篇 |
1980年 | 26篇 |
1979年 | 11篇 |
1978年 | 14篇 |
1977年 | 13篇 |
1976年 | 13篇 |
1974年 | 14篇 |
1973年 | 11篇 |
排序方式: 共有3740条查询结果,搜索用时 15 毫秒
191.
Brands M Grande YC Endermann R Gahlmann R Krüger J Raddatz S 《Bioorganic & medicinal chemistry letters》2003,13(16):2641-2645
We report the synthesis and pharmacological evaluation of new derivatives of the natural dipeptide antibiotic TAN 1057 A,B containing heterocycles either in the beta-amino acid side chain or as mimics of the urea function. In the course of this program, we identified novel analogues that display activity towards a broader panel of Gram-positive bacteriae. 相似文献
192.
Kiefmann R Heckel K Dörger M Schenkat S Stoeckelhuber M Wesierska-Gadek J Goetz AE 《American journal of physiology. Lung cellular and molecular physiology》2003,285(5):L996-L1005
During systemic inflammation, recruitment and activation of leukocytes in the pulmonary microcirculation may result in a potentially life-threatening acute lung injury. We elucidated the role of the poly(ADP-ribose) synthetase (PARS), a nucleotide-polymerizing enzyme, in the regulation of leukocyte recruitment within the lung with regard to the localization in the pulmonary microcirculation and in correlation to hemodynamics in the respective vascular segments and expression of intercellular adhesion molecule 1 during endotoxemia. Inhibition of PARS by 3-aminobenzamide reduced the endotoxin-induced leukocyte recruitment within pulmonary arterioles, capillaries, and venules in rabbits as quantified by in vivo fluorescence microscopy. Microhemodynamics and thus shear rates in all pulmonary microvascular segments remained constant. Simultaneously, inhibition of PARS with 3-aminobenzamide suppressed the endotoxin-induced adhesion molecules expression as demonstrated for intercellular adhesion molecule 1 by immunohistochemistry and Western blot analysis. We confirmed this result with the use of PARS knockout mice. The inhibitory effect of 3-aminobenzamide on leukocyte recruitment was associated with a reduction of pulmonary capillary leakage and edema formation. We first provide evidence that PARS activation mediates the leukocyte sequestration in pulmonary microvessels through upregulation of adhesion molecules. As reactive oxygen species released from leukocyte are supposed to cause an upregulation of adhesion molecules we conclude that PARS inhibition contributes to termination of this vicious cycle and inhibits the inflammatory process. 相似文献
193.
Merkl R 《Journal of molecular evolution》2003,57(4):453-466
Unequal use of synonymous codons has been found in several prokaryotic and eukaryotic genomes. This bias has been associated with translational efficiency. The prevalence of this bias across lineages is currently unknown. Here, a new method (GCB) to measure codon usage bias is presented. It uses an iterative approach for the determination of codon scores and allows the computation of an index of codon bias suitable for interspecies comparison. A server to calculate GCB-values of individual genes as well as a list of compiled results are available at
. The method was applied to complete bacterial genomes. The relation of codon usage bias with amino acid composition and the choice of stop codons were determined and discussed. 相似文献
194.
195.
Changes in the elastic properties of single deoxyribonucleic acid (DNA) molecules in the presence of different DNA-binding agents are identified using atomic force microscope single molecule force spectroscopy. We investigated the binding of poly(dG-dC) dsDNA with the minor groove binder distamycin A, two supposed major groove binders, an alpha-helical and a 3(10)-helical peptide, the intercalants daunomycin, ethidium bromide and YO, and the bis-intercalant YOYO. Characteristic mechanical fingerprints in the overstretching behavior of the studied single DNA-ligand complexes were observed allowing the distinction between different binding modes. Docking of ligands to the minor or major groove of DNA has the effect that the intramolecular B-S transition remains visible as a distinct plateau in the force-extension trace. By contrast, intercalation of small molecules into the double helix is characterized by the vanishing of the B-S plateau. These findings lead to the conclusion that atomic force microscope force spectroscopy can be regarded as a single molecule biosensor and is a potent tool for the characterization of binding motives of small ligands to DNA. 相似文献
196.
Jäggi RD Franco-Obregón A Mühlhäusser P Thomas F Kutay U Ensslin K 《Biophysical journal》2003,84(1):665-670
The nuclear pore complex (NPC) represents the only pathway for macromolecular communication between the nuclear and cytoplasmic compartments of the cell. Nucleocytoplasmic transport requires the interaction of transport receptors with phenylalanine-glycine (FG)-repeats that line the transport pathway through the NPC. Here we examine the effects of transport receptors and amphipathic alcohols on NPC topology using scanning force microscopy. We show that transport receptors that irreversibly bind FG-repeats increase NPC vertical aspect, whereas transport receptors that weakly interact with FG-repeats increase NPC diameter. Interestingly, small polar alcohols likewise increase NPC diameter. These opposing effects agree with the inhibition or enhancement of nuclear transport, respectively, previously ascribed to these agents. 相似文献
197.
198.
199.
Liebel U Starkuviene V Erfle H Simpson JC Poustka A Wiemann S Pepperkok R 《FEBS letters》2003,554(3):394-398
A modular microscope-based screening platform, with applications in large-scale analysis of protein function in intact cells is described. It includes automated sample preparation, image acquisition, data management and analysis, and the genome-wide automated retrieval of bioinformatic information. The modular nature of the system ensures that it is rapidly adaptable to new biological questions or sets of proteins. Two automated functional assays addressing protein secretion and the integrity of the Golgi complex were developed and tested. This shows the potential of the system in large-scale, cell-based functional proteomic projects. 相似文献
200.
The isolated N-terminal domain of the glucagon-like peptide-1 (GLP-1) receptor binds exendin peptides with much higher affinity than GLP-1 总被引:4,自引:0,他引:4
López de Maturana R Willshaw A Kuntzsch A Rudolph R Donnelly D 《The Journal of biological chemistry》2003,278(12):10195-10200
Two fragments of the receptor for glucagon-like peptide-1 (GLP-1), each containing the N-terminal domain, were expressed and characterized in either bacterial or mammalian cells. The first fragment, rNT-TM1, included the N-terminal domain and first transmembrane helix and was stably expressed in the membrane of human embryonic kidney 293 cells. The second, 6H-rNT, consisted of only the N-terminal domain of the receptor fused with a polyhistidine tag at its N terminus. The latter fragment was expressed in Escherichia coli in the form of inclusion bodies from which the protein was subsequently purified and refolded in vitro. Although both receptor fragments displayed negligible (125)I-labeled GLP-1(7-36)amide-specific binding, they both displayed high affinity for the radiolabeled peptide antagonist (125)I-exendin-4(9-39). Competition binding studies demonstrated that the N-terminal domain of the GLP-1 receptor maintains high affinity for the agonist exendin-4 as well as the antagonists exendin-4(3-39) and exendin-4(9-39) whereas, in contrast, GLP-1 affinity was greatly reduced. This study shows that although the exendin antagonists are not dependent upon the extracellular loops and transmembrane helices for maintaining their normal high affinity binding, the endogenous agonist GLP-1 requires regions outside of the N-terminal domain. Hence, distinct structural features in exendin-4, between residues 9 and 39, provide additional affinity for the N-terminal domain of the receptor. These data are consistent with a model for the binding of peptide ligands to the GLP-1 receptor in which the central and C-terminal regions of the peptides bind to the N terminus of the receptor, whereas the N-terminal residues of peptide agonists interact with the extracellular loops and transmembrane helices. 相似文献