全文获取类型
收费全文 | 2900篇 |
免费 | 154篇 |
出版年
2023年 | 6篇 |
2022年 | 15篇 |
2021年 | 39篇 |
2020年 | 17篇 |
2019年 | 30篇 |
2018年 | 49篇 |
2017年 | 26篇 |
2016年 | 55篇 |
2015年 | 86篇 |
2014年 | 107篇 |
2013年 | 186篇 |
2012年 | 231篇 |
2011年 | 212篇 |
2010年 | 129篇 |
2009年 | 111篇 |
2008年 | 202篇 |
2007年 | 207篇 |
2006年 | 185篇 |
2005年 | 172篇 |
2004年 | 203篇 |
2003年 | 169篇 |
2002年 | 197篇 |
2001年 | 20篇 |
2000年 | 23篇 |
1999年 | 26篇 |
1998年 | 31篇 |
1997年 | 33篇 |
1996年 | 39篇 |
1995年 | 30篇 |
1994年 | 31篇 |
1993年 | 25篇 |
1992年 | 17篇 |
1991年 | 21篇 |
1990年 | 13篇 |
1989年 | 13篇 |
1988年 | 12篇 |
1987年 | 13篇 |
1986年 | 7篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 10篇 |
1982年 | 9篇 |
1981年 | 9篇 |
1980年 | 10篇 |
1979年 | 6篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 4篇 |
1970年 | 2篇 |
1969年 | 2篇 |
排序方式: 共有3054条查询结果,搜索用时 15 毫秒
901.
902.
Thp is a large deletion on chromosome 17 which includes the maternal lethal gene Tme. Documentation of inheritance patterns suggests that Tme is an imprinted gene which is required for viability; maternal deletion is lethal while paternal deletion is viable. However, paternal transmission of Thp is rarely the expected 50%. We show here that paternally inherited Thp is lethal in some strains, providing evidence of an incompletely penetrant, dosage sensitive lethal allele of a locus that probably maps to the hairpin tail region of chr. 17. Interpretation of the various phenotypes associated with loss of the putative Tme gene, lgf2r, may need to be revised in view of these observations. Dev Genet 20:23–28, 1997. © 1997 Wiley-Liss, Inc. 相似文献
903.
Suppression of Heme Oxygenase-1 mRNA Expression by Interferon-γ in
Human Glioblastoma Cells 总被引:1,自引:0,他引:1
Kazuhiro Takahashi Masaharu Nakayama Kazuhisa Takeda Hiroyoshi Fujita & Shigeki Shibahara 《Journal of neurochemistry》1999,72(6):2356-2361
Heme oxygenase is a rate-limiting enzyme in heme catabolism that cleaves heme to form biliverdin, carbon monoxide, and iron. Heme oxygenase-1 is an inducible isozyme and is expressed in many types of cells and tissues. Large amounts of these heme degradation products may be noxious to the host, especially in the brain. We therefore searched for the factors that suppress the expression of heme oxygenase-1. Northern blot analysis showed that treatment with interferon-gamma and with interleukin-1beta for 24 h decreased the expression levels of heme oxygenase-1 mRNA to approximately 20 and approximately 50% of the control levels, respectively, in a human glioblastoma cell line, T98G. Treatment with a combination of these two cytokines additively decreased the expression levels of heme oxygenase-1 mRNA. Western blot analysis showed that the expression level of heme oxygenase-1 protein was also decreased by treatment with interferon-gamma, but not with interleukin-1beta. Moreover, pretreatment with interferon-gamma partially suppressed the induction of heme oxygenase-1 mRNA expression caused by either sodium nitroprusside, cadmium, or hemin. These findings raise the possibility that the expression of heme oxygenase-1 is down-regulated by interferon-gamma in the nervous system. 相似文献
904.
905.
Salvatore Santamaria Daniel R. Martin Xiangyi Dong Kazuhiro Yamamoto Suneel S. Apte Josefin Ahnstrm 《The Journal of biological chemistry》2021,297(5)
A disintegrin-like and metalloprotease domain with thrombospondin type 1 motifs (ADAMTS)8 is a secreted protease, which was recently implicated in pathogenesis of pulmonary arterial hypertension (PAH). However, the substrate repertoire of ADAMTS8 and regulation of its activity are incompletely understood. Although considered a proteoglycanase because of high sequence similarity and close phylogenetic relationship to the proteoglycan-degrading proteases ADAMTS1, 4, 5, and 15, as well as tight genetic linkage with ADAMTS15 on human chromosome 11, its aggrecanase activity was reportedly weak. Several post-translational factors are known to regulate ADAMTS proteases such as autolysis, inhibition by endogenous inhibitors, and receptor-mediated endocytosis, but their impacts on ADAMTS8 are unknown. Here, we show that ADAMTS8 undergoes autolysis at six different sites within its spacer domain. We also found that in contrast to ADAMTS4 and 5, ADAMTS8 levels were not regulated through low-density lipoprotein receptor-related protein 1 (LRP1)-mediated endocytosis. Additionally, ADAMTS8 lacked significant activity against the proteoglycans aggrecan, versican, and biglycan. Instead, we found that ADAMTS8 cleaved osteopontin, a phosphoprotein whose expression is upregulated in PAH. Multiple ADAMTS8 cleavage sites were identified using liquid chromatography–tandem mass spectrometry. Osteopontin cleavage by ADAMTS8 was efficiently inhibited by TIMP-3, an endogenous inhibitor of ADAMTS1, 4, and 5, as well as by TIMP-2, which has no previously reported inhibitory activity against other ADAMTS proteases. These differences in post-translational regulation and substrate repertoire differentiate ADAMTS8 from other family members and may help to elucidate its role in PAH. 相似文献
906.
Takayuki Iriyama Kohsuke Takeda Hiromi Nakamura Yoshifumi Morimoto Takumi Kuroiwa Junya Mizukami Tsuyoshi Umeda Takuya Noguchi Isao Naguro Hideki Nishitoh Kaoru Saegusa Kei Tobiume Toshiki Homma Yutaka Shimada Hitoshi Tsuda Satoshi Aiko Issei Imoto Johji Inazawa Kazuhiro Chida Yoshimasa Kamei Shiro Kozuma Yuji Taketani Atsushi Matsuzawa Hidenori Ichijo 《The EMBO journal》2009,28(7):843-853
Apoptosis and inflammation generally exert opposite effects on tumorigenesis: apoptosis serves as a barrier to tumour initiation, whereas inflammation promotes tumorigenesis. Although both events are induced by various common stressors, relatively little is known about the stress‐induced signalling pathways regulating these events in tumorigenesis. Here, we show that stress‐activated MAP3Ks, ASK1 and ASK2, which are involved in cellular responses to various stressors such as reactive oxygen species, differentially regulate the initiation and promotion of tumorigenesis. ASK2 in cooperation with ASK1 functioned as a tumour suppressor by exerting proapoptotic activity in epithelial cells, which was consistent with the reduction in ASK2 expression in human cancer cells and tissues. In contrast, ASK1‐dependent cytokine production in inflammatory cells promoted tumorigenesis. Our findings suggest that ASK1 and ASK2 are critically involved in tumorigenesis by differentially regulating apoptosis and inflammation. 相似文献
907.
Ohtsu K Hirano HY Tsutsumi N Hirai A Nakazono M 《Molecular genetics and genomics : MGG》2005,274(6):606-615
A new type of transposon, named Anaconda (Anac) has been found in rice (Oryza sativa). In this paper, we demonstrate that Anaconda elements have diversified by acquisition of host cellular genes, amplification of the elements, and substitution and deletion
of short segments. We identified four Anaconda elements in studies of rice alternative oxidase (AOX) genes, and subsequently isolated an additional 23 elements based on the identity of their terminal inverted repeats (TIRs).
The Anaconda elements have long TIRs (114–458 bp). They also have direct repeats of 9 or 10 bp in their flanking regions that are thought
to have been generated upon transposition. These structural features reveal that the Anaconda elements belong to the Mu superfamily. The most prominent feature of the Anaconda elements is the high frequency with which they have acquired host cellular genes. Of the 27 elements found here, 19 appear
to have sequences presumably derived from rice genes, for example, the genes for AOX1c (four elements), cytochrome P450 (five
elements), l-asparaginase (five elements), and PCF8 (two elements). Four elements, AnacA1–A4, have both the AOX1c and P450 genes. One element, AnacB14, involves a gene similar to mudrA of maize MuDR. Database analyses revealed that the loci of 26 of the 27 Anaconda elements in the subspecies japonica are the same as those in the subspecies indica. This suggests that these elements were incorporated before the divergence of these two subspecies. 相似文献
908.
Irie K Masuda A Shindo M Nakagawa Y Ohigashi H 《Bioorganic & medicinal chemistry》2004,12(17):4575-4583
Recent investigations discovered nonkinase-type phorbol ester receptors, RasGRPs, chimaerins, and Unc13s. Phorbol ester binding occurs at the cysteine-rich sequences of about 50 residues in the C1 domains of these receptors. Fifty-one-residue RasGRP C1 peptides except for RasGRP2 showed significant phorbol 12,13-dibutyrate (PDBu) binding, but the K(d) values of the RasGRP1 and RasGRP3 C1 peptides were about 10-fold larger than those for the corresponding whole enzymes. Addition of the C-terminal basic amino acid cluster decreased their K(d) values about 10-fold, suggesting that the positive charges of these C1 peptides play an important role in the PDBu binding in the presence of negatively-charged phosphatidylserine. The 51-mer chimaerin C1 peptides showed potent PDBu binding, while the Unc13 and Munc13-1 C1 peptides without sufficient positive charges hardly bound PDBu. By the rapid screening system using this C1 peptide library, 5-prenyl-indolactam-V was identified as a promising lead for the novel protein kinase C isozyme specific ligands. 相似文献
909.
Suzuki S Numakawa T Shimazu K Koshimizu H Hara T Hatanaka H Mei L Lu B Kojima M 《The Journal of cell biology》2004,167(6):1205-1215
Brain-derived neurotrophic factor (BDNF) plays an important role in synaptic plasticity but the underlying signaling mechanisms remain unknown. Here, we show that BDNF rapidly recruits full-length TrkB (TrkB-FL) receptor into cholesterol-rich lipid rafts from nonraft regions of neuronal plasma membranes. Translocation of TrkB-FL was blocked by Trk inhibitors, suggesting a role of TrkB tyrosine kinase in the translocation. Disruption of lipid rafts by depleting cholesterol from cell surface blocked the ligand-induced translocation. Moreover, disruption of lipid rafts prevented potentiating effects of BDNF on transmitter release in cultured neurons and synaptic response to tetanus in hippocampal slices. In contrast, lipid rafts are not required for BDNF regulation of neuronal survival. Thus, ligand-induced TrkB translocation into lipid rafts may represent a signaling mechanism selective for synaptic modulation by BDNF in the central nervous system. 相似文献
910.