全文获取类型
收费全文 | 445篇 |
免费 | 32篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 1篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 6篇 |
2017年 | 2篇 |
2016年 | 8篇 |
2015年 | 15篇 |
2014年 | 11篇 |
2013年 | 30篇 |
2012年 | 21篇 |
2011年 | 30篇 |
2010年 | 10篇 |
2009年 | 29篇 |
2008年 | 27篇 |
2007年 | 34篇 |
2006年 | 44篇 |
2005年 | 34篇 |
2004年 | 45篇 |
2003年 | 28篇 |
2002年 | 42篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 9篇 |
1997年 | 6篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 6篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1989年 | 2篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
排序方式: 共有477条查询结果,搜索用时 93 毫秒
21.
Akao Y Maruyama W Shimizu S Yi H Nakagawa Y Shamoto-Nagai M Youdim MB Tsujimoto Y Naoi M 《Journal of neurochemistry》2002,82(4):913-923
The role of mitochondrial permeability transition (PT) in apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol [NM(R)Sal], was studied by use of dopaminergic neuroblastoma SH-SY5Y cells. NM(R)Sal reduced mitochondrial membrane potential, DeltaPsim, in the early phase of apoptosis, which was not suppressed by a pan-caspase inhibitor, but was antagonized by Bcl-2 and cyclosporin A, suggesting the involvement of the PT in NM(R)Sal-induced loss of DeltaPsim. NM(R)Sal-induced apoptosis was completely inhibited not only by Bcl-2 and a pan-caspase inhibitor, but also by cyclosporin A, suggesting the essential role of the PT in NM(R)Sal-induced apoptosis. In mitochondria isolated from rat liver, NM(R)Sal induced swelling and reduced DeltaPsim, which was inhibited by cyclosporin A and Bcl-2 overexpression. These results indicate that NM(R)Sal induced the PT by direct action on the mitochondria. Rasagiline, N-propargyl-1(R)-aminoindan, which is a now under a clinical trial for Parkinson's disease, suppressed the DeltaPsim reduction, release of cytochrome c, and apoptosis induced by NM(R)Sal in SH-SY5Y cells. Rasagiline also inhibited the NM(R)Sal-induced loss of DeltaPsim and swelling in the isolated mitochondria, proving that rasagiline directly targets the mitochondria also. Altogether, mitochondrial PT plays a key role both in NM(R)Sal-induced cell death and the neuroprotective effect of rasagiline. 相似文献
22.
Nakamura N Miyake Y Matsushita M Tanaka S Inoue H Kanazawa H 《Journal of biochemistry》2002,132(3):483-491
Kinesin family proteins are microtubule-dependent molecular motors involved in the intracellular motile process. Using a Ca2+ -binding protein, CHP (calcineurin B homologous protein), as a bait for yeast two hybrid screening, we identified a novel kinesin-related protein, KIF1Bbeta2. KIF1Bbeta2 is a member of the KIF1 subfamily of kinesin-related proteins, and consists of an amino terminal KIF1B-type motor domain followed by a tail region highly similar to that of KIF1A. CHP binds to regions adjacent to the motor domains of KIF1Bbeta2 and KIF1B, but not to those of the other KIF1 family members, KIF1A and KIF1C. Immunostaining of neuronal cells showed that a significant portion of KIF1Bbeta2 is co-localized with synaptophysin, a marker protein for synaptic vesicles, but not with a mitochondria-staining dye. Subcellular fractionation analysis indicated the co-localization of KIF1Bbeta2 with synaptophysin. These results suggest that KIF1Bbeta2, a novel CHP-interacting molecular motor, mediates the transport of synaptic vesicles in neuronal cells. 相似文献
23.
Molecular analysis of gene expression in the developing pontocerebellar projection system 总被引:7,自引:0,他引:7
Díaz E Ge Y Yang YH Loh KC Serafini TA Okazaki Y Hayashizaki Y Speed TP Ngai J Scheiffele P 《Neuron》2002,36(3):417-434
As an approach toward understanding the molecular mechanisms of neuronal differentiation, we utilized DNA microarrays to elucidate global patterns of gene expression during pontocerebellar development. Through this analysis, we identified groups of genes specific to neuronal precursor cells, associated with axon outgrowth, and regulated in response to contact with synaptic target cells. In the cerebellum, we identified a phase of granule cell differentiation that is independent of interactions with other cerebellar cell types. Analysis of pontine gene expression revealed that distinct programs of gene expression, correlated with axon outgrowth and synapse formation, can be decoupled and are likely influenced by different cells in the cerebellar target environment. Our approach provides insight into the genetic programs underlying the differentiation of specific cell types in the pontocerebellar projection system. 相似文献
24.
Hata K Andoh A Shimada M Fujino S Bamba S Araki Y Okuno T Fujiyama Y Bamba T 《American journal of physiology. Gastrointestinal and liver physiology》2002,282(6):G1035-G1044
Colonic subepithelial myofibroblasts (SEMFs) may play a role in the modulation of mucosal inflammatory responses. We investigated the effects of interleukin (IL)-17 on IL-6 and chemokine [IL-8 and monocyte chemoattractant protein (MCP)-1] secretion in colonic SEMFs. Cytokine expression was determined by ELISA and Northern blotting. Nuclear factor kappa B (NF-kappaB) DNA-binding activity was evaluated by electrophortetic gel mobility shift assay (EMSA). The activation of mitogen-activated protein kinase (MAPK) was assessed by immunoblotting. IL-6, IL-8, and MCP-1 secretions were rapidly induced by IL-17. IL-17 induced NF-kappaB activation within 45 min after stimulation. A blockade of NF-kappaB activation markedly reduced these responses. MAPK inhibitors (SB-203580, PD-98059, and U-0126) significantly reduced the IL-17-induced IL-6 and chemokine secretion. The combination of either IL-17 + IL-1beta or IL-17 + tumor necrosis factor (TNF)-alpha enhanced cytokine secretion; in particular, the effects of IL-17 + TNF-alpha on IL-6 secretion were much stronger than the other responses. This was dependent on the enhancement of IL-6 mRNA stability. In conclusion, human SEMFs secreted IL-6, IL-8, and MCP-1 in response to IL-17. These responses might play an important role in the pathogenesis of gut inflammation. 相似文献
25.
26.
Konishi A Shimizu S Hirota J Takao T Fan Y Matsuoka Y Zhang L Yoneda Y Fujii Y Skoultchi AI Tsujimoto Y 《Cell》2003,114(6):673-688
It is poorly understood how apoptotic signals arising from DNA damage are transmitted to mitochondria, which release apoptogenic factors into the cytoplasm that activate downstream destruction programs. Here, we identify histone H1.2 as a cytochrome c-releasing factor that appears in the cytoplasm after exposure to X-ray irradiation. While all nuclear histone H1 forms are released into the cytoplasm in a p53-dependent manner after irradiation, only H1.2, but not other H1 forms, induced cytochrome c release from isolated mitochondria in a Bak-dependent manner. Reducing H1.2 expression enhanced cellular resistance to apoptosis induced by X-ray irradiation or etoposide, but not that induced by other stimuli including TNF-alpha and UV irradiation. H1.2-deficient mice exhibited increased cellular resistance in thymocytes and the small intestine to X-ray-induced apoptosis. These results indicate that histone H1.2 plays an important role in transmitting apoptotic signals from the nucleus to the mitochondria following DNA double-strand breaks. 相似文献
27.
Bamba S Andoh A Yasui H Makino J Kim S Fujiyama Y 《American journal of physiology. Gastrointestinal and liver physiology》2003,285(3):G529-G538
IL-11 inhibits the activation of NF-kappaB and induces the Th2 polarization of CD4+ T cells. The clinical utility of IL-11 is being investigated in Crohn's disease. However, physiological secretion of IL-11 in the intestine remains unclear. In this study, we investigated IL-11 secretion in human intestinal subepithelial myofibroblasts (SEMFs). Intestinal SEMFs were isolated from the human colonic mucosa. IL-11 secretion and mRNA expression were determined by ELISA and Northern blot analysis. The activating protein (AP)-1-DNA binding activity was evaluated by EMSA. IL-11 secretion was induced by IL-1beta and transforming growth factor (TGF)-beta1. These were also observed at the mRNA level. The EMSAs demonstrated that both IL-1beta and TGF-beta1 induced AP-1 activation within 2 h after stimulation, and a blockade of AP-1 activation by the recombinant adenovirus containing a dominant negative c-Jun markedly reduced the IL-1beta- and TGF-beta1-induced IL-11 mRNA expression. IL-1beta and TGF-beta1 induced an activation of ERK p42/44 and p38 MAP kinases, and the MAP kinase inhibitors (SB-202190, PD-98059, and U-0216) significantly reduced the IL-1beta- and TGF-beta1-induced IL-11 secretion. The upregulation of IL-11 mRNA by IL-1beta- and TGF-beta1 was also mediated by a p38 MAP kinase-mediated mRNA stabilization. The combination of IL-1beta and TGF-beta1 additively enhanced IL-11 secretion. Intestinal SEMFs secreted IL-11 in response to IL-1beta- and TGF-beta1. Mucosal IL-11 secretion might be important as an anti-inflammatory response in the pathogenesis of intestinal inflammation. 相似文献
28.
Masayuki Mori Shingo Akiyoshi Yosuke Mizuno Hisato Okuizumi Yasushi Okazaki Yoshihide Hayashizaki Masahiko Nishimura 《Mammalian genome》1998,9(9):695-709
We have applied the restriction landmark genomic scanning (RLGS) method to the SMXA recombinant inbred (RI) mouse strain
set to reveal its detailed genetic profile. A total of 663 polymorphic RLGS spot loci were identified, 576 of which were assigned
to chromosomes. Strain distribution patterns (SDPs) at 55 microsatellite marker loci were also obtained. As a result, the
total number of loci with distinct SDPs on chromosomes increased to 400. These loci were dispersed on all chromosomes, except
for the Chromosome (Chr) Y, and effectively covered the genome with an average spacing of 4 cM. The SMXA RI strain set, hereby,
would be of value for genetic study.
Received: 20 February 1998 / Accepted: 19 May 1998 相似文献
29.
Yuichi Sugahara Shingo Akiyoshi Yasushi Okazaki Yoshihide Hayashizaki Isao Tanihata 《Mammalian genome》1998,9(8):643-651
The RLGS (Restriction Landmark Genome Scanning) method was originally developed as a powerful method for enabling viewing
of thousands of restriction landmarks. It offers a tool for obtaining information about genetic loci, with a single RLGS profile
displaying approximately 2000 restriction landmarks as spots. One of the most useful applications is RLGS spot mapping, which
allows the efficient, low-cost construction of the genetic map of any organism. However, analyses of the profiles depend mainly
on human visual observation and are tedious and laborious. Although several commercially available image analyzing systems
for profile comparison have been examined, they cannot be used for the RLGS spot mapping system owing to the background characteristics
of the RLGS profiles, unsatisfactory rates of correspondence, and inefficient correction of informative genetic data. We therefore
developed a novel automatic image analysis system for RLGS spot mapping, using an original algorithm based on the binary image
transferred from the original RLGS profile. This system was employed for identifying non-polymorphic and parental strain-specific
polymorphic spots of the F1 mouse profile and yielded efficient initial screening of RLGS profiles.
Received: 5 December 1997 / Accepted: 6 April 1998 相似文献
30.
High-efficiency cloning of
Arabidopsis
full-length cDNA by biotinylated CAP trapper 总被引:17,自引:5,他引:12
Motoaki Seki Piero Carninci Yoko Nishiyama Yoshihide Hayashizaki Kazuo Shinozaki 《The Plant journal : for cell and molecular biology》1998,15(5):707-720
Full-length cDNAs are essential for functional analysis of plant genes. We constructed high-content, full-length cDNA libraries from Arabidopsis thaliana plants based on chemical introduction of a biotin group into the diol residue of the CAP structure of eukaryotic mRNA, followed by RNase I treatment, to select full-length cDNA. More than 90% of the total clones obtained were of full length; recombinant clones were obtained with high efficiency (2.2 × 106/9 μg starting mRNA). Sequence analysis of 111 randomly picked clones indicated that 32 isolated cDNA groups were derived from novel genes in the A. thaliana genome. 相似文献