全文获取类型
收费全文 | 373篇 |
免费 | 37篇 |
专业分类
410篇 |
出版年
2023年 | 2篇 |
2021年 | 5篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 6篇 |
2017年 | 4篇 |
2016年 | 6篇 |
2015年 | 23篇 |
2014年 | 10篇 |
2013年 | 20篇 |
2012年 | 30篇 |
2011年 | 18篇 |
2010年 | 14篇 |
2009年 | 8篇 |
2008年 | 14篇 |
2007年 | 17篇 |
2006年 | 20篇 |
2005年 | 18篇 |
2004年 | 10篇 |
2003年 | 12篇 |
2002年 | 12篇 |
2001年 | 9篇 |
2000年 | 10篇 |
1999年 | 6篇 |
1998年 | 6篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 6篇 |
1993年 | 2篇 |
1992年 | 9篇 |
1991年 | 8篇 |
1990年 | 11篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1987年 | 8篇 |
1986年 | 6篇 |
1985年 | 8篇 |
1983年 | 3篇 |
1981年 | 2篇 |
1979年 | 8篇 |
1978年 | 2篇 |
1977年 | 5篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1972年 | 5篇 |
1971年 | 4篇 |
1970年 | 2篇 |
1969年 | 4篇 |
1967年 | 3篇 |
排序方式: 共有410条查询结果,搜索用时 15 毫秒
11.
Dissecting the contributions of GC content and codon usage to gene expression in the model alga Chlamydomonas reinhardtii 下载免费PDF全文
Rouhollah Barahimipour Daniela Strenkert Juliane Neupert Michael Schroda Sabeeha S. Merchant Ralph Bock 《The Plant journal : for cell and molecular biology》2015,84(4):704-717
The efficiency of gene expression in all organisms depends on the nucleotide composition of the coding region. GC content and codon usage are the two key sequence features known to influence gene expression, but the underlying molecular mechanisms are not entirely clear. Here we have determined the relative contributions of GC content and codon usage to the efficiency of nuclear gene expression in the unicellular green alga Chlamydomonas reinhardtii. By comparing gene variants that encode an identical amino acid sequence but differ in their GC content and/or codon usage, we show that codon usage is the key factor determining translational efficiency and, surprisingly, also mRNA stability. By contrast, unfavorable GC content affects gene expression at the level of the chromatin structure by triggering heterochromatinization. We further show that mutant algal strains that permit high‐level transgene expression are less susceptible to epigenetic transgene suppression and do not establish a repressive chromatin structure at the transgenic locus. Our data disentangle the relationship between GC content and codon usage, and suggest simple strategies to overcome the transgene expression problem in Chlamydomonas. 相似文献
12.
Nitrosation and oxidation in the regulation of gene expression. 总被引:19,自引:0,他引:19
13.
Hervé Chneiweiss François Hirsch Lluis Montoliu Albrecht M. Müller Solveig Fenet Marion Abecassis Jennifer Merchant Bernard Baertschi Mylène Botbol-Baum James A. Houghton Mihalis Kritikos Janet Mifsud Ewa Bartnik Johannes Rath Christiane Druml Bärbel Friedrich Ana Sofia Carvalho Dirk Lanzerath Agnès Saint-Raymond 《Transgenic research》2017,26(5):709-713
In this consensus paper resulting from a meeting that involved representatives from more than 20 European partners, we recommend the foundation of an expert group (European Steering Committee) to assess the potential benefits and draw-backs of genome editing (off-targets, mosaicisms, etc.), and to design risk matrices and scenarios for a responsible use of this promising technology. In addition, this European steering committee will contribute in promoting an open debate on societal aspects prior to a translation into national and international legislation. 相似文献
14.
15.
Elisa Greggio Jean-Marc Taymans Eugene Yuejun Zhen Renée Vancraenenbroeck Peng Sun Howard Jaffe Kalpana Merchant 《Biochemical and biophysical research communications》2009,389(3):449-454
Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of inherited Parkinson’s disease (PD). The protein is large and complex, but pathogenic mutations cluster in a region containing GTPase and kinase domains. LRRK2 can autophosphorylate in vitro within a dimer pair, although the significance of this reaction is unclear. Here, we mapped the sites of autophosphorylation within LRRK2 and found several potential phosphorylation sites within the GTPase domain. Using mass spectrometry, we found that Thr1343 is phosphorylated and, using kinase dead versions of LRRK2, show that this is an autophosphorylation site. However, we also find evidence for additional sites in the GTPase domain and in other regions of the protein suggesting that there may be multiple autophosphorylation sites within LRRK2. These data suggest that the kinase and GTPase activities of LRRK2 may exhibit complex autoregulatory interdependence. 相似文献
16.
Ingersoll SB Stoltzfus GP Merchant MH Ahmad S Edwards CR Ahmed A Oyer JL Finkler NJ Holloway RW Edwards JR 《Cytotherapy》2012,14(6):716-723
Background/AimsThe aim of this study was to compare the cytotoxic response against ovarian cancer (OC) cells elicited by different immune effector cells in combination with the cytokines interleukin (IL)-2 and interferon (IFN) α-2b.MethodsOC cells were co-cultured with peripheral blood mononuclear cells (PBMC) from normal donors or OC patients and IL-2 or IFN α-2b alone or in combination, in order to determine the cytotoxicity. T cells were isolated from healthy donors to determine T cell cytotoxic activity. PBMC from healthy donors and OC patients were expanded in an IL-2/IL-7/IL-12 cocktail with and without anti-CD3 antibody, and the cytotoxic activity measured. Flow cytometry was performed on primary, selected and expanded cells to determine T, B, and natural killer- (NK) cell percentages.ResultsHealthy donor PBMC elicited a significant cytotoxic response (59%) compared with OC patient PBMC (7%). T cells enriched from normal donors elicited a significant cytotoxic response (18%) compared with controls lacking effector cells (1.4%); however, the cytotoxicity observed was significantly less compared with unselected PBMC. Expanded effector cells consisted primarily of T cells (98%) and the fold-expansion was significantly higher in the presence of anti-CD3 (19- versus 132-fold). No significant difference in the expansion (either fold-expansion or cell type) was observed between OC patients and healthy donors. Expanded cells from both healthy donors and OC patients elicited a significant cytotoxic response in the presence of IL-2 (19% and 22%) compared with controls.ConclusionsPBMC from OC patients do not elicit a significant cytotoxic response; however, ex vivo-expanded cells from OC patients are capable of cytotoxic killing similar to unexpanded T cells isolated from normal donors. These data provide the groundwork for further development of cellular therapy against OC. 相似文献
17.
Kao JY Pierzchala A Rathinavelu S Zavros Y Tessier A Merchant JL 《Regulatory peptides》2006,134(1):23-29
Somatostatin is a regulatory peptide found in abundance in the stomach. We have previously shown that somatostatin is required for IL-4-mediated resolution of Helicobacter pylori gastritis. In the current study, we hypothesize that somatostatin acts directly on antigen-presenting cells in the stomach to lessen the severity of gastritis. To test this hypothesis, we first show that CD11c+ dendritic cells are present in the infected tissue of mice with H. pylori-induced gastritis. Pretreatment of bone marrow-derived dendritic cells with somatostatin results in decreased IL-12 production, and lower splenocyte proliferation induced by H. pylori-stimulated dendritic cells. Furthermore, octreotide, a somatostatin analogue, is more potent than somatostatin in suppressing IL-12 release by H. pylori-stimulated dendritic cells through an NF-kappaB-independent pathway. In addition, IL-4 stimulates somatostatin secretion from dendritic cells. In conclusion, somatostatin inhibits dendritic cell activation by H. pylori; a possible mechanism by which IL-4 mediates resolution of gastritis. We suggest that octreotide may be effective in treating immune-mediated diseases of the stomach. 相似文献
18.
A newly discovered family of small proteins in the yeast mitochondrial intermembrane space mediates import of hydrophobic proteins from the cytoplasm into the inner membrane. Loss of one of these chaperone-like proteins from human mitochondria results in a disease that causes deafness, muscle weakness and blindness. 相似文献
19.
Regulated copper uptake in Chlamydomonas reinhardtii in response to copper availability. 总被引:1,自引:0,他引:1 下载免费PDF全文
A saturable and temperature-dependent copper uptake pathway has been identified in Chlamydomonas reinhardtii. The uptake system has a high affinity for copper ions (Km approximately 0.2 microM) and is more active in cells that are adapted to copper deficiency than to cells grown in a medium containing physiological (submicromolar to micromolar) copper ion concentrations. The maximum velocity of copper uptake by copper-deficient cells (169 pmol h-1 10(6) cells-1 or 62 ng min-1 mg-1 chlorophyll) is up to 20-fold greater than that of fully copper-supplemented cells, and the Km (approximately 2 x 10(2) nM) is unaffected. Thus, the same uptake system appears to operate in both copper-replete and copper-deficient cells, but its expression or activity must be induced under copper-deficient conditions. A cupric reductase activity is also increased in copper-deficient compared with copper-sufficient cells. The physiological characteristics of the regulation of this cupric reductase are compatible with its involvement in the uptake pathway. Despite the operation of the uptake pathway under both copper-replete and copper-deficient conditions, C. reinhardtii cells maintained in fully copper-supplemented cells do not accumulate copper in excess of their metabolic need. These results provide evidence for a homeostatic mechanism for copper metabolism in C. reinhardtii. 相似文献
20.