全文获取类型
收费全文 | 1607篇 |
免费 | 146篇 |
专业分类
1753篇 |
出版年
2023年 | 5篇 |
2022年 | 17篇 |
2021年 | 28篇 |
2020年 | 16篇 |
2019年 | 19篇 |
2018年 | 31篇 |
2017年 | 23篇 |
2016年 | 53篇 |
2015年 | 72篇 |
2014年 | 95篇 |
2013年 | 100篇 |
2012年 | 146篇 |
2011年 | 123篇 |
2010年 | 88篇 |
2009年 | 79篇 |
2008年 | 120篇 |
2007年 | 126篇 |
2006年 | 101篇 |
2005年 | 104篇 |
2004年 | 75篇 |
2003年 | 72篇 |
2002年 | 91篇 |
2001年 | 16篇 |
2000年 | 14篇 |
1999年 | 19篇 |
1998年 | 31篇 |
1997年 | 11篇 |
1996年 | 12篇 |
1995年 | 8篇 |
1994年 | 6篇 |
1993年 | 14篇 |
1992年 | 6篇 |
1991年 | 6篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1971年 | 1篇 |
1969年 | 2篇 |
1968年 | 1篇 |
排序方式: 共有1753条查询结果,搜索用时 10 毫秒
971.
Pérez-Martín M Grondona JM Cifuentes M Pérez-Fígares JM Jiménez JA Fernández-Llebrez P 《Cell and tissue research》2000,300(1):11-19
By gently scraping off the surface of the lateral ventricles of adult bovine brains, we obtained sheets containing the ependymal layer and some attached sub-ependymal cells. Explants were cultured in serum-free medium or in two media enriched with 20% fetal calf serum or 20% adult bovine cerebrospinal fluid, and processed for different time intervals from 4 h to 60 days. For characterization of the ependymal cells we used antisera against S-100 protein, vimentin and glial fibrillary acidic protein (GFAP). For comparison, the ependyma of adult bovines and of fetuses from days 60 to 120 post coitum was studied in situ. The adult ependyma consisted of a ciliated, cuboid cell monolayer with short basal processes; it displayed S-100 immunoreactivity but only scarce deposits of vimentin and no GFAP. The fetal ependyma had the appearance of a pseudostratified epithelium with elongated nuclei and basal processes containing S-100 and vimentin from day 80 post coitum and GFAP from day 100 post coitum. In explants, no differences were seen between the three culture media; the ependyma became pseudostratified, developed basal processes and showed increasing amounts of S-100 and vimentin first, and subsequently also GFAP. These changes were concomitant with the onset of mitotic activity in the subependymal layer leading to the production of numerous cells. The morphological and immunocytochemical features of ependymal cells in cultured explants resembled those of fetal ependyma. Our results indicate that the culture of ependymal explants from adult bovine lateral ventricles is an useful model system for morphological and functional studies of the ependyma and for the analysis of cell proliferation in the subependymal layer. 相似文献
972.
Serrano M Robatzek S Torres M Kombrink E Somssich IE Robinson M Schulze-Lefert P 《The Journal of biological chemistry》2007,282(9):6803-6811
We describe an experimental setup using submerged cultures of Arabidopsis seedlings in 96-well microtiter plates that permits chemical intervention of rapid elicitor-mediated immune responses. Screening of a chemical library comprising 120 small molecules with known biological activities revealed four compounds reducing cellulysin- or flg22-activated gene expression of the early pathogen-associated molecular patterns (PAMP)-responsive ATL2 gene. One chemical, oxytriazine, was found to induce ATL2 gene expression in the absence of PAMP. By monitoring additional flg22-triggered immediate early plant responses, we present evidence that two compounds, triclosan and fluazinam, interfere with the accumulation of reactive oxygen species and internalization of the activated plasma membrane resident FLS2 immune receptor. Using triclosan structure types and enzyme activity inhibition assays, Arabidopsis MOD1 enoyl-acyl carrier protein reductase, a subunit of the fatty-acid synthase type II (FAS II) complex, was identified as a likely cellular target of triclosan. Inhibition of all tested elicitor-triggered early immune responses by triclosan indicates a potential role for signaling lipids in flg22-triggered immunity. Chemical profiling of eca mutants, each showing deregulated ATL2 gene expression, with the identified compounds revealed mutantspecific response patterns and allowed us to deduce tentative action sites of ECA genes relative to the compound targets. 相似文献
973.
974.
Chubanov V Schlingmann KP Wäring J Heinzinger J Kaske S Waldegger S Mederos y Schnitzler M Gudermann T 《The Journal of biological chemistry》2007,282(10):7656-7667
Hypomagnesemia with secondary hypocalcemia is an autosomal recessive disorder caused by mutations in the TRPM6 gene. Current experimental evidence suggests that TRPM6 may function in a specific association with TRPM7 by means of heterooligomeric channel complex formation. Here, we report the identification and functional characterization of a new hypomagnesemia with secondary hypocalcemia missense mutation in TRPM6. The affected subject presented with profound hypomagnesemia and hypocalcemia caused by compound heterozygous mutation in the TRPM6 gene: 1208(-1)G > A affecting the acceptor splice site preceding exon 11, and 3050C > G resulting in the amino acid change (P1017R) in the putative pore-forming region of TRPM6. To assess the functional consequences of the P1017R mutation, TRPM6(P1017R) and wild-type TRPM6 were co-expressed with TRPM7 in Xenopus oocytes and HEK 293 cells, and currents were assessed by two-electrode voltage clamp and whole cell patch clamp measurements, respectively. Co-expression of wild-type TRPM6 and TRPM7 resulted in a significant increase in the amplitude of TRPM7-like currents. In contrast, TRPM6(P1017R) suppressed TRPM7 channel activity. In line with these observations, TRPM7, containing the corresponding mutation P1040R, displayed a dominant-negative effect upon co-expression with wild-type TRPM7. Confocal microscopy and fluorescence resonance energy transfer recordings demonstrated that the P1017R mutation neither affects assembly of TRPM6 with TRPM7, nor co-trafficking of heteromultimeric channel complexes to the cell surface. We conclude that a functional defect in the putative pore of TRPM6/7 channel complexes is sufficient to impair body magnesium homeostasis. 相似文献
975.
Transfer of the molybdenum cofactor synthesized by Rhodobacter capsulatus MoeA to XdhC and MobA 总被引:1,自引:0,他引:1
The molybdenum cofactor (Moco) exists in different variants in the cell and can be directly inserted into molybdoenzymes utilizing the molybdopterin (MPT) form of Moco. In bacteria such as Rhodobacter capsulatus and Escherichia coli, MPT is further modified by attachment of a GMP nucleotide, forming MPT guanine dinucleotide (MGD). In this work, we analyzed the distribution and targeting of different forms of Moco to their respective user enzymes by proteins that bind Moco and are involved in its further modification. The R. capsulatus proteins MogA, MoeA, MobA, and XdhC were purified, and their specific interactions were analyzed. Interactions between the protein pairs MogA-MoeA, MoeA-XdhC, MoeA-MobA, and XdhC-MobA were identified by surface plasmon resonance measurements. In addition, the transfer of Moco produced by the MogA-MoeA complex to XdhC was investigated. A direct competition of MobA and XdhC for Moco binding was determined. In vitro analyses showed that XdhC bound to MobA, prevented the binding of Moco to MobA, and thereby inhibited MGD biosynthesis. The data were confirmed by in vivo studies in R. capsulatus cells showing that overproduction of XdhC resulted in a 50% decrease in the activity of bis-MGD-containing Me(2)SO reductase. We propose that, in bacteria, the distribution of Moco in the cell and targeting to the respective user enzymes are accomplished by specific proteins involved in Moco binding and modification. 相似文献
976.
Phosphorylation-regulated cleavage of the reticulon protein Nogo-B by caspase-7 at a noncanonical recognition site 总被引:1,自引:0,他引:1
Schweigreiter R Stasyk T Contarini I Frauscher S Oertle T Klimaschewski L Huber LA Bandtlow CE 《Proteomics》2007,7(24):4457-4467
Reticulons (RTNs) are a large family of transmembrane proteins present throughout the eukaryotic domain in virtually every cell type. Despite their wide distribution, their function is still mostly unknown. RTN4, also termed Nogo, comes in three isoforms, Nogo-A, -B, and -C. While Nogo-A has been described as potent inhibitor of nerve growth, Nogo-B has been implicated in vascular remodeling and regulation of apoptosis. We show here that Nogo-B gets cleaved by caspase-7, but not caspase-3, during apoptosis at a caspase nonconsensus site. By a combination of MS and site-directed mutagenesis we demonstrate that proteolytic processing of Nogo-B is regulated by phosphorylation of Ser(16) within the cleavage site. We present cyclin-dependent kinase (Cdk)1 and Cdk2 as kinases that phosphorylate Nogo-B at Ser(16) in vitro. In vivo, cleavage of Nogo-B is markedly increased in Schwann cells in a lesion model of the rat sciatic nerve. Taken together, we identified an RTN protein as one out of a selected number of caspase targets during apoptosis and as a novel substrate for Cdk1 and 2. Furthermore, our data support a functionality of caspase-7 that is distinct from closely related caspase-3. 相似文献
977.
978.
979.
980.