全文获取类型
收费全文 | 396篇 |
免费 | 40篇 |
专业分类
436篇 |
出版年
2021年 | 4篇 |
2019年 | 3篇 |
2018年 | 3篇 |
2017年 | 10篇 |
2016年 | 7篇 |
2015年 | 4篇 |
2014年 | 13篇 |
2013年 | 18篇 |
2012年 | 26篇 |
2011年 | 20篇 |
2010年 | 18篇 |
2009年 | 14篇 |
2008年 | 19篇 |
2007年 | 13篇 |
2006年 | 13篇 |
2005年 | 15篇 |
2004年 | 11篇 |
2003年 | 12篇 |
2002年 | 8篇 |
2001年 | 9篇 |
2000年 | 10篇 |
1999年 | 10篇 |
1998年 | 12篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 3篇 |
1991年 | 13篇 |
1990年 | 9篇 |
1989年 | 3篇 |
1988年 | 6篇 |
1987年 | 12篇 |
1986年 | 6篇 |
1985年 | 8篇 |
1984年 | 5篇 |
1983年 | 6篇 |
1982年 | 4篇 |
1981年 | 5篇 |
1977年 | 5篇 |
1976年 | 3篇 |
1975年 | 5篇 |
1972年 | 3篇 |
1971年 | 7篇 |
1970年 | 5篇 |
1969年 | 3篇 |
1967年 | 2篇 |
1937年 | 2篇 |
1925年 | 4篇 |
排序方式: 共有436条查询结果,搜索用时 15 毫秒
11.
DNA-dependent RNA polymerase has been isolated from Rhodomicrobium vannielii. Like those from other eubacteria, the enzyme contained four subunits: beta and beta prime (Mr 155,000), alpha (Mr 38,000), and sigma (Mr 98,000). Analysis by isoelectric focussing showed that both alpha and sigma had several forms with different isoelectric pH values. The enzyme was sensitive to rifampicin (5 ng rifampicin ml-1 gave 50% inhibition) and capable of specific promoter selection with DNA from R. vannielii, calf thymus and phage T7D111. 相似文献
12.
13.
14.
Peter Schemmer Zhi Zhong Uwe Galli Michael D. Wheeler Li Xiangli Blair U. Bradford Lars O. Conzelmann Dow Forman José Boyer Ronald G. Thurman 《Amino acids》2013,44(3):925-931
It has been demonstrated that a wide variety of white blood cells and macrophages (i.e. Kupffer cells, alveolar and peritoneal macrophages and neutrophils) contain glycine-gated chloride channels. Binding of glycine on the receptor stimulates Cl? influx causing membrane hyperpolarization that prevents agonist-induced influx of calcium. Since platelet-aggregation is calcium-dependent, this study was designed to test the hypothesis that glycine would inhibit platelet aggregation. Rats were fed diets rich of glycine for 5 days, while controls received isonitrogenous valine. The bleeding time and ADP- and collagen-induced platelet aggregation were measured. Dietary glycine significantly increased bleeding time about twofold compared to valine-treated controls. Furthermore, the amplitude of platelet aggregation stimulated with ADP or collagen was significantly decreased in whole blood drawn from rats fed 2.5 or 5 % dietary glycine by over 50 %. Addition of glycine in vitro (1–10 mM) also blunted rat platelet aggregation in a dose-dependent manner. Strychnine, a glycine receptor antagonist, abrogated the inhibitory effect of glycine on platelet-aggregation in vitro suggesting the glycine works via a glycine receptor. Glycine also blunted aggregation of human platelets. Further, the glycine receptor was detected in both rat and human platelets by western blotting. Based on these data, it is concluded that glycine prevents aggregation of platelets in a dose-dependent manner via mechanisms involving a glycine receptor. 相似文献
15.
16.
Classification and nomenclature of all human homeobox genes 总被引:2,自引:0,他引:2
Background
The homeobox genes are a large and diverse group of genes, many of which play important roles in the embryonic development of animals. Increasingly, homeobox genes are being compared between genomes in an attempt to understand the evolution of animal development. Despite their importance, the full diversity of human homeobox genes has not previously been described.Results
We have identified all homeobox genes and pseudogenes in the euchromatic regions of the human genome, finding many unannotated, incorrectly annotated, unnamed, misnamed or misclassified genes and pseudogenes. We describe 300 human homeobox loci, which we divide into 235 probable functional genes and 65 probable pseudogenes. These totals include 3 genes with partial homeoboxes and 13 pseudogenes that lack homeoboxes but are clearly derived from homeobox genes. These figures exclude the repetitive DUX1 to DUX5 homeobox sequences of which we identified 35 probable pseudogenes, with many more expected in heterochromatic regions. Nomenclature is established for approximately 40 formerly unnamed loci, reflecting their evolutionary relationships to other loci in human and other species, and nomenclature revisions are proposed for around 30 other loci. We use a classification that recognizes 11 homeobox gene 'classes' subdivided into 102 homeobox gene 'families'.Conclusion
We have conducted a comprehensive survey of homeobox genes and pseudogenes in the human genome, described many new loci, and revised the classification and nomenclature of homeobox genes. The classification scheme may be widely applicable to homeobox genes in other animal genomes and will facilitate comparative genomics of this important gene superclass. 相似文献17.
Jagjeet S. Mnpotra Zhuanhong Qiao Jian Cai Diane L. Lynch Alan Grossfield Nicholas Leioatts Dow P. Hurst Michael C. Pitman Zhao-Hui Song Patricia H. Reggio 《The Journal of biological chemistry》2014,289(29):20259-20272
In this study, we applied a comprehensive G protein-coupled receptor-Gαi protein chemical cross-linking strategy to map the cannabinoid receptor subtype 2 (CB2)- Gαi interface and then used molecular dynamics simulations to explore the dynamics of complex formation. Three cross-link sites were identified using LC-MS/MS and electrospray ionization-MS/MS as follows: 1) a sulfhydryl cross-link between C3.53(134) in TMH3 and the Gαi C-terminal i-3 residue Cys-351; 2) a lysine cross-link between K6.35(245) in TMH6 and the Gαi C-terminal i-5 residue, Lys-349; and 3) a lysine cross-link between K5.64(215) in TMH5 and the Gαi α4β6 loop residue, Lys-317. To investigate the dynamics and nature of the conformational changes involved in CB2·Gi complex formation, we carried out microsecond-time scale molecular dynamics simulations of the CB2 R*·Gαi1β1γ2 complex embedded in a 1-palmitoyl-2-oleoyl-phosphatidylcholine bilayer, using cross-linking information as validation. Our results show that although molecular dynamics simulations started with the G protein orientation in the β2-AR*·Gαsβ1γ2 complex crystal structure, the Gαi1β1γ2 protein reoriented itself within 300 ns. Two major changes occurred as follows. 1) The Gαi1 α5 helix tilt changed due to the outward movement of TMH5 in CB2 R*. 2) A 25° clockwise rotation of Gαi1β1γ2 underneath CB2 R* occurred, with rotation ceasing when Pro-139 (IC-2 loop) anchors in a hydrophobic pocket on Gαi1 (Val-34, Leu-194, Phe-196, Phe-336, Thr-340, Ile-343, and Ile-344). In this complex, all three experimentally identified cross-links can occur. These findings should be relevant for other class A G protein-coupled receptors that couple to Gi proteins. 相似文献
18.
Garrett T. Dow Michel Gilbert James B. Thoden Hazel M. Holden 《Protein science : a publication of the Protein Society》2017,26(3):586-599
Campylobacter jejuni is a Gram‐negative bacterium that represents a leading cause of human gastroenteritis worldwide. Of particular concern is the link between C. jejuni infections and the subsequent development of Guillain‐Barré syndrome, an acquired autoimmune disorder leading to paralysis. All Gram‐negative bacteria contain complex glycoconjugates anchored to their outer membranes, but in most strains of C. jejuni, this lipoglycan lacks the O‐antigen repeating units. Recent mass spectrometry analyses indicate that the C. jejuni 81116 (Penner serotype HS:6) lipoglycan contains two dideoxyhexosamine residues, and enzymological assay data show that this bacterial strain can synthesize both dTDP‐3‐acetamido‐3,6‐dideoxy‐d ‐glucose and dTDP‐3‐acetamido‐3,6‐dideoxy‐d ‐galactose. The focus of this investigation is on WlaRG from C. jejuni, which plays a key role in the production of these unusual sugars by functioning as a pyridoxal 5′‐phosphate dependent aminotransferase. Here, we describe the first three‐dimensional structures of the enzyme in various complexes determined to resolutions of 1.7 Å or higher. Of particular significance are the external aldimine structures of WlaRG solved in the presence of either dTDP‐3‐amino‐3,6‐dideoxy‐d ‐galactose or dTDP‐3‐amino‐3,6‐dideoxy‐d ‐glucose. These models highlight the manner in which WlaRG can accommodate sugars with differing stereochemistries about their C‐4′ carbon positions. In addition, we present a corrected structure of WbpE, a related sugar aminotransferase from Pseudomonas aeruginosa, solved to 1.3 Å resolution. 相似文献
19.
Communication with a growing family: diffusible signal factor (DSF) signaling in bacteria 总被引:1,自引:0,他引:1
Many pathogenic bacteria use cell-cell signaling to regulate the expression of factors contributing to virulence. Bacteria produce signals of diverse structural classes. The signal molecule known as diffusible signal factor (DSF) is a cis-unsaturated fatty acid that was first described in the plant pathogen Xanthomonas campestris. Recent work has shown that structurally related molecules produced by the unrelated bacteria Burkholderia cenocepacia and Pseudomonas aeruginosa regulate virulence, biofilm formation and antibiotic tolerance in these important human pathogens. Furthermore, DSF family signals have been shown to be involved in interspecies signaling that modulates bacterial behavior. An understanding of these diverse signaling mechanisms could suggest strategies for interference, with consequences for disease control. 相似文献
20.
The Helicobacter pylori adhesin protein HopQ exploits the dimer interface of human CEACAMs to facilitate translocation of the oncoprotein CagA 下载免费PDF全文
Daniel A Bonsor Qing Zhao Barbara Schmidinger Evelyn Weiss Jingheng Wang Daniel Deredge Robert Beadenkopf Blaine Dow Wolfgang Fischer Dorothy Beckett Patrick L Wintrode Rainer Haas Eric J Sundberg 《The EMBO journal》2018,37(13)
Helicobacter pylori infects half of the world's population, and strains that encode the cag type IV secretion system for injection of the oncoprotein CagA into host gastric epithelial cells are associated with elevated levels of cancer. CagA translocation into host cells is dependent on interactions between the H. pylori adhesin protein HopQ and human CEACAMs. Here, we present high‐resolution structures of several HopQ‐CEACAM complexes and CEACAMs in their monomeric and dimeric forms establishing that HopQ uses a coupled folding and binding mechanism to engage the canonical CEACAM dimerization interface for CEACAM recognition. By combining mutagenesis with biophysical and functional analyses, we show that the modes of CEACAM recognition by HopQ and CEACAMs themselves are starkly different. Our data describe precise molecular mechanisms by which microbes exploit host CEACAMs for infection and enable future development of novel oncoprotein translocation inhibitors and H. pylori‐specific antimicrobial agents. 相似文献