全文获取类型
收费全文 | 235篇 |
免费 | 15篇 |
国内免费 | 1篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 6篇 |
2019年 | 5篇 |
2018年 | 3篇 |
2017年 | 5篇 |
2016年 | 4篇 |
2015年 | 7篇 |
2014年 | 11篇 |
2013年 | 6篇 |
2012年 | 10篇 |
2011年 | 6篇 |
2010年 | 12篇 |
2009年 | 12篇 |
2008年 | 12篇 |
2007年 | 15篇 |
2006年 | 21篇 |
2005年 | 12篇 |
2004年 | 15篇 |
2003年 | 18篇 |
2002年 | 14篇 |
2001年 | 9篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 6篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1988年 | 1篇 |
1986年 | 3篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1965年 | 1篇 |
排序方式: 共有251条查询结果,搜索用时 15 毫秒
11.
Inoue H Tsukita K Iwasato T Suzuki Y Tomioka M Tateno M Nagao M Kawata A Saido TC Miura M Misawa H Itohara S Takahashi R 《The EMBO journal》2003,22(24):6665-6674
Mutant copper/zinc superoxide dismutase (SOD1)-overexpressing transgenic mice, a mouse model for familial amyotrophic lateral sclerosis (ALS), provides an excellent resource for developing novel therapies for ALS. Several observations suggest that mitochondria-dependent apoptotic signaling, including caspase-9 activation, may play an important role in mutant SOD1-related neurodegeneration. To elucidate the role of caspase-9 in ALS, we examined the effects of an inhibitor of X chromosome-linked inhibitor of apoptosis (XIAP), a mammalian inhibitor of caspase-3, -7 and -9, and p35, a baculoviral broad caspase inhibitor that does not inhibit caspase-9. When expressed in spinal motor neurons of mutant SOD1 mice using transgenic techniques, XIAP attenuated disease progression without delaying onset. In contrast, p35 delayed onset without slowing disease progression. Moreover, caspase-9 was activated in spinal motor neurons of human ALS subjects. These data strongly suggest that caspase-9 plays a crucial role in disease progression of ALS and constitutes a promising therapeutic target. 相似文献
12.
Hisashi Koike Zen Kouchi Tadatoshi Kinouchi Tatsuya Maeda Hiroyuki Sorimachi Takaomi C. Saido Kei Maruyama Akira Okuyama Koichi Suzuki Shoichi Ishiura 《Cytotechnology》2000,33(1-3):213-219
Thimet oligopeptidase (TOP) is a thiol- andmetallo-dependent peptidase and has been shown to beone of the -secretase candidates. TOPexpressed in COS cells cleaved amyloid precursorprotein (APP) at the -secretase site, and wefound a proteolytic product of APP called secretedform of APP by -secretase (sAPP) in theconditioned media. Here we demonstrate thatsAPP was increased in conditioned media whenTOP was coexpressed in COS cells with APP and treatedwith an ADAM inhibitor SI-27. In addition, althoughTOP expressed in COS cell was localized at nuclei orGolgi apparatus, it exclusively colocalized at Golgiapparatus when APP was coexpressed with TOP. 相似文献
13.
Shinji Sudoh Yuuki Kawamura Shinji Sato §Rong Wang ‡Takaomi C. Saido †Fumitaka Oyama Yoshiyuki Sakaki Hiroto Komano Katsuhiko Yanagisawa 《Journal of neurochemistry》1998,71(4):1535-1543
Abstract: Mutations in the presenilin genes PS1 and PS2 cause the most common form of early-onset familial Alzheimer's disease. The influence of PS1 mutations on the generation of endogenous intracellular amyloid β-protein (Aβ) species was assessed using a highly sensitive immunoblotting technique with inducible mouse neuro-blastoma (Neuro 2a) cell lines expressing the human wild-type (wt) or mutated PS1 (M146L or Δexon 10). The induction of mutated PS1 increased the intracellular levels of two distinct Aβ species ending at residue 42 that were likely to be Aβ1–42 and its N-terminally truncated variant(s) Aβx-42. The induction of mutated PS1 resulted in a higher level of intracellular Aβ1–42 than of intracellular Aβx-42, whereas extracellular levels of Aβ1–42 and Aβx-42 were increased proportionally. In addition, the intracellular generation of these Aβ42 species in wt and mutated PS1 -induced cells was completely blocked by brefeldin A, whereas it exhibited differential sensitivities to monensin: the increased accumulation of intracellular Aβx-42 versus inhibition of intracellular Aβ1–42 generation. These data strongly suggest that Aβx-42 is generated in a proximal Golgi, whereas Aβ1–42 is generated in a distal Golgi and/or a post-Golgi compartment. Thus, it appears that PS1 mutations enhance the degree of 42-specific γ-secretase cleavage that occurs in the normal β-amyloid precursor protein processing pathway (a) in the endoplasmic reticulum or the early Golgi apparatus prior to β-secretase cleavage or (b) in the distinct sites where Aβx-42 and Aβ1–42 are generated. 相似文献
14.
15.
Yasuyuki Ishida Hiroaki Yokoi Shinichi Isomura Hajime Ohtani Shin Tsuge Tatsuki Sekino Masami Nakanishi Takashi Kimoto 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1998,716(1-2)
Pyrolysis–gas chromatography (Py–GC) combined with on-line methylation was applied to a correlation analysis between the distributions of fatty acid components in the lipids of zooplankter individuals and those of ingested algae using principal component analysis (PCA). Py–GC in the presence of organic alkali, tetramethylammonium hydroxide (TMAH), was used to estimate the apparent distributions of fatty acid components contained in a single individual zooplankter weighing several tens of micrograms and a small sample size of ingested algae samples in the order of 10 μg. The observed fatty acid compositions were used as a database for the PCA in order to discriminate the zooplankton and ingested algae samples. The result obtained indicated that the fatty acid compositions of zooplankton individuals used in this work were significantly reflected in those of their ingested food in spite of some contribution from isomerization and/or elongation of fatty acid components during digestion of the ingested algae phytoplankton in living zooplankters. 相似文献
16.
Ariko Miyake Takaomi Ishida Makoto Yamagishi Takuma Hara Kazuo Umezawa Toshiki Watanabe Ryouichi Horie 《Microbes and infection / Institut Pasteur》2010,12(5):400-408
Previous reports indicate that nuclear factor (NF)-κB regulates induction of human immunodeficiency virus type 1 (HIV-1) gene expression in latently infected cells. However, the role of NF-κB in cells with active HIV-1 replication is not well understood. In this study, we examined the effect of a new NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on HIV-1 replication in a human T cell line and phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PHA-PBMCs). We further explored the mechanism of DHMEQ-mediated inhibition of HIV-1 replication. DHMEQ inhibited HIV-1 replication in HIV-1-infected Molt-4 and PHA-PBMCs. DHMEQ inhibited constitutive NF-κB activity in HIV-1-infected PHA-PBMCs and HIV long terminal repeat promoter activity driven by tumor necrosis factor (TNF)-α and the trans-activator Tat. The single-round assay using vesicular stomatitis virus-pseudotyped virus in the human T cell line M8166 indicated that DHMEQ treatment resulted in decreased integration of HIV-1 provirus into the host genome and decreased HIV-1 expression. These results indicate that NF-κB regulates early events as well as the initial and accelerated expression of HIV-1 in its life cycle. Therefore, we conclude that NF-κB is a molecular target for controlling active HIV-1 replication. 相似文献
17.
18.
19.
20.