全文获取类型
收费全文 | 810篇 |
免费 | 64篇 |
国内免费 | 1篇 |
出版年
2023年 | 4篇 |
2022年 | 7篇 |
2021年 | 10篇 |
2020年 | 16篇 |
2019年 | 13篇 |
2018年 | 15篇 |
2017年 | 18篇 |
2016年 | 22篇 |
2015年 | 47篇 |
2014年 | 34篇 |
2013年 | 49篇 |
2012年 | 42篇 |
2011年 | 51篇 |
2010年 | 24篇 |
2009年 | 24篇 |
2008年 | 36篇 |
2007年 | 41篇 |
2006年 | 38篇 |
2005年 | 42篇 |
2004年 | 55篇 |
2003年 | 40篇 |
2002年 | 47篇 |
2001年 | 10篇 |
2000年 | 10篇 |
1999年 | 12篇 |
1998年 | 15篇 |
1997年 | 11篇 |
1996年 | 9篇 |
1995年 | 10篇 |
1994年 | 8篇 |
1993年 | 4篇 |
1992年 | 4篇 |
1991年 | 8篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1983年 | 4篇 |
1982年 | 12篇 |
1981年 | 5篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1972年 | 3篇 |
1970年 | 4篇 |
1969年 | 3篇 |
1962年 | 3篇 |
1960年 | 3篇 |
排序方式: 共有875条查询结果,搜索用时 0 毫秒
51.
Sorting nexins (Snxs) are a recently discovered family of conserved hydrophilic cytoplasmic proteins that have been found associated with membranes of the endocytic system and that are implicated in the trafficking of many endosomal membrane proteins, including the epidermal growth factor receptor and transferrin receptor. Snx proteins are partly defined by the presence of a p40 phox homology domain that has recently been shown to bind phosphatidylinositol 3-phosphate. Most Snx proteins also contain a predicted coiled-coils domain in the carboxyl-terminal half of the protein and have been shown to form dimers with other members of the Snx family. The yeast sorting nexins Vps5p and Vps17p form a dimer and are also components of the retromer complex that mediates endosome-to-Golgi transport of the carboxypeptidase Y receptor Vps10p. To functionally define the different domains of the yeast sorting nexins Vps5p and Vps17p, we have generated various truncations to examine the role that the different domains of Vps5p/Vps17p play in their respective functions. Herein, we show that the C-terminal halves of Vps5p and Vps17p, which contain the coiled-coils domains, are necessary and sufficient for their interaction. We have also mapped the retromer assembly domain to the N-terminal half of Vps5p and found that binding of Vps5p by Vps17p synergizes the interaction between Vps5p and other retromer components. Additionally, we have examined which domain(s) of Vps5p is necessary for membrane association. 相似文献
52.
Bjerknes M Cheng H 《American journal of physiology. Gastrointestinal and liver physiology》2002,283(3):G767-G777
Previous studies of chimeric animals demonstrate that multipotential stem cells play a role in the development of the gastric epithelium; however, despite much effort, it is not clear whether they persist into adulthood. Here, chemical mutagenesis was used to label random epithelial cells by loss of transgene function in adult hemizygous ROSA26 mice, a mouse strain expressing the transgene lacZ in all tissues. Many clones derived from such cells contained all the major epithelial cell types, thereby demonstrating existence of functional multipotential stem cells in adult mouse gastric epithelium. We also observed clones containing only a single mature cell type, indicating the presence of long-lived committed progenitors in the gastric epithelium. Similar results were obtained in duodenum and colon, showing that this mouse model is suitable for lineage tracing in all regions of the gastrointestinal tract and likely useful for cell lineage studies in other adult renewing tissues. 相似文献
53.
Several neuropsychiatric disorders map to human 15q13-q14, which contains a strong candidate in the alpha7-nicotinic acetylcholine receptor subunit gene (CHRNA7) and is partly duplicated, complicating further genetic analysis. We have shown that the partial duplication is in a hybrid (CHRFAM7A)between CHRNA7 and one of many copies of a novel gene (FAM7A). We have constructed a 3-Mb map of 15q13-q14 showing that CHRFAM7A is part of a large segmental duplication in the opposite orientation to CHRNA7 and revealing several other duplications. The data support a model of recent evolutionary events including duplications, at least one large deletion, and an inversion. We have identified two individuals with a structure that lacks CHRFAM7A and therefore predates many steps in this model, suggesting an unstable region with other intermediates possibly still in existence. This instability may be relevant to the many neuropsychiatric disorders that map in this region. 相似文献
54.
55.
Wilson JS Hazel SM Williams NJ Phiri A French NP Hart CA 《Applied and environmental microbiology》2003,69(7):4312-4315
Eighteen (72%) of 25 badger social groups were found to excrete Salmonella enterica serovar Ried, S. enterica serovar Binza, S. enterica serovar Agama, or S. enterica serovar Lomita. Each serovar was susceptible to a panel of antimicrobials. Based on results of pulsed-field gel electrophoresis, the S. enterica serovar Agama and S. enterica serovar Binza isolates were very similar, but two clones each of S. enterica serovar Lomita and S. enterica serovar Ried were found. Badgers excreting S. enterica serovar Agama were spatially clustered. 相似文献
56.
57.
Hazel M Holden James B Thoden Frank M Raushel 《Current opinion in structural biology》1998,8(6):679-685
The direct transfer of metabolites from one protein to another in a biochemical pathway or between one active site and another within a single enzyme has been described as substrate channeling. The first structural visualization of such a phenomenon was provided by the X-ray crystallographic analysis of tryptophan synthase, in which a tunnel of approximately 25 Å in length was observed. The recently determined three-dimensional structure of carbamoyl phosphate synthetase sets a new long distance record in that the three active sites are separated by nearly 100 Å. 相似文献
58.
Mesalazine is widely used in the treatment of inflammatory bowel disease. Little is known about the dose-response relationship and about possible dose related side effects. In ulcerative colitis higher dosages of mesalazine (3 g) are more effective in maintaining a remission than lower dosages (1.5 g). In mild to moderately active ulcerative colitis, studies also indicate that higher dosages might be more effective in inducing remission. Dose-comparing studies in Crohn''s disease are even more sparse, but the available results indicate higher efficacy at higher dose levels. None of the known side effects of mesalazine are clearly dose-related. A pH-dependent release system, however, can cause a sudden release of high doses of mesalazine. Consequent peak levels in serum have been implicated in mesalazine induced nephrotoxicity. In conclusion, despite the current practice of using increasing dosages of mesalazine in inflammatory bowel disease, both efficacy and safety have been established tentatively. 相似文献
59.
Steven G. Smith Kaatje Smits Simone A. Joosten Krista E. van Meijgaarden Iman Satti Helen A. Fletcher Nadia Caccamo Francesco Dieli Francoise Mascart Helen McShane Hazel M. Dockrell Tom H. M. Ottenhoff TBVI TB Biomarker Working Group 《PloS one》2015,10(9)
Intracellular cytokine staining combined with flow cytometry is one of a number of assays designed to assess T-cell immune responses. It has the specific advantage of enabling the simultaneous assessment of multiple phenotypic, differentiation and functional parameters pertaining to responding T-cells, most notably, the expression of multiple effector cytokines. These attributes make the technique particularly suitable for the assessment of T-cell immune responses induced by novel tuberculosis vaccines in clinical trials. However, depending upon the particular nature of a given vaccine and trial setting, there are approaches that may be taken at different stages of the assay that are more suitable than other alternatives. In this paper, the Tuberculosis Vaccine Initiative (TBVI) TB Biomarker Working group reports on efforts to assess the conditions that will determine when particular assay approaches should be employed. We have found that choices relating to the use of fresh whole blood or peripheral blood mononuclear cells (PBMC) and frozen PBMC; use of serum-containing or serum-free medium; length of stimulation period and use of co-stimulatory antibodies can all affect the sensitivity of intracellular cytokine assays. In the case of sample material, frozen PBMC, despite some loss of sensitivity, may be more advantageous for batch analysis. We also recommend that for multi-site studies, common antibody panels, gating strategies and analysis approaches should be employed for better comparability. 相似文献
60.
Andreea Oana Mocanu Anny Mulya Hazel Huang Olivia Dan Hideharu Shimizu Esam Batayyah Stacy A. Brethauer Anca Dinischiotu John P. Kirwan 《PloS one》2015,10(10)