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排序方式: 共有264条查询结果,搜索用时 15 毫秒
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Berberine alters the processing of Alzheimer's amyloid precursor protein to decrease Abeta secretion 总被引:2,自引:0,他引:2
Asai M Iwata N Yoshikawa A Aizaki Y Ishiura S Saido TC Maruyama K 《Biochemical and biophysical research communications》2007,352(2):498-502
Berberine is an isoquinoline alkaloid isolated from Coptidis rhizoma, a major herb widely used in Chinese herbal medicine. Berberine's biological activity includes antidiarrheal, antimicrobial, and anti-inflammatory effects. Recent findings show that berberine prevents neuronal damage due to ischemia or oxidative stress and that it might act as a novel cholesterol-lowering compound. The accumulation of amyloid-beta peptide (Abeta) derived from amyloid precursor protein (APP) is a triggering event leading to the pathological cascade of Alzheimer's disease (AD); therefore the inhibition of Abeta production should be a rational therapeutic strategy in the prevention and treatment of AD. Here, we report that berberine reduces Abeta levels by modulating APP processing in human neuroglioma H4 cells stably expressing Swedish-type of APP at the range of berberine concentration without cellular toxicity. Our results indicate that berberine would be a promising candidate for the treatment of AD. 相似文献
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Daisuke Sawada Tomoyuki Katayama Yuya Tsukuda Nozomi Saito Masashi Takano Hiroshi Saito Ken-ichiro Takagi Eiji Ochiai Seiichi Ishizuka Kazuya Takenouchi Atsushi Kittaka 《Bioorganic & medicinal chemistry letters》2009,19(18):5397-5400
We synthesized and isolated 2α-substituted analogs of 14-epi-previtamin D3 after thermal isomerization at 80 °C for the first time. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the 2α-methyl-substituted analog was found to have greater genomic activity than 14-epi-previtamin D3. 相似文献
45.
Immortalized bovine brain cell lines provide ideal in vitro cellular infection models for bovine spongiform encephalopathies (BSEs) caused by prions without enduring species barrier. We have established an immortalized brain cell line (FBBC-1 cells) from primary cultures of cryopreserved fetal bovine brain tissues after transfection with SV40 large T antigen. FBBC-1 cells are stable after passaging to >100 population doublings after single cell cloning, with a generation time of 24 h. After the treatment with dibutyryl-cyclic AMP, the cells ceased proliferation and extended neurite-like processes that were immunostained with the antibody against tubulin βIII, a marker of immature neurons. Upregulation of tubulin βIII expression was confirmed by immunoblotting. These bovine cells expressed cellular prion protein and its processed smaller C1 fragment, and may provide an in vitro means of propagating cattle BSE prion. 相似文献
46.
Sato K Minegishi S Takano J Plattner F Saito T Asada A Kawahara H Iwata N Saido TC Hisanaga S 《Journal of neurochemistry》2011,117(3):504-515
Cyclin-dependent kinase 5 (Cdk5) is a Ser/Thr kinase that is activated by binding to its regulatory subunit, p35. The calpain-mediated cleavage of p35 to p25 and the resulting aberrant activity and neurotoxicity of Cdk5 have been implicated in neurological disorders, such as Alzheimer's disease. To gain further insight into the molecular mechanisms underlying the pathological function of Cdk5, we investigated the role of the calpain inhibitor protein calpastatin (CAST), in controlling the aberrant production of p25. For this purpose, brain tissue from wild-type, CAST-over-expressing (transgenic), and CAST knockout mice were analyzed. Cleavage of p35 to p25 was increased in extracts from CAST knockout mice, compared with wild-type. Conversely, generation of p25 was not detected in brain lysates from CAST-over-expressing mice. CAST expression was 5-fold higher in mouse cerebellum than cerebral cortex. Accordingly, p25 production was lower in the cerebellum than the cerebral cortex. Furthermore, the Ca(2+) -dependent degradation of p35 by proteasome was evident when calpain was inhibited. Taken together, these results suggest that CAST is a crucial regulator of calpain activity, the production of p25, and, hence, the deregulation of Cdk5. Therefore, impairment of CAST expression and its associated mechanisms may contribute to the pathogenesis of neurodegenerative disorders. 相似文献
47.
Casein Kinase 2 dependent phosphorylation of eIF4B regulates BACE1 expression in Alzheimer’s disease
Barbara Bettegazzi Laura Sebastian Monasor Serena Bellani Franca Codazzi Lisa Michelle Restelli Alessio Vittorio Colombo Nikolaus Deigendesch Stephan Frank Takashi Saito Takaomi C. Saido Sven Lammich Sabina Tahirovic Fabio Grohovaz Daniele Zacchetti 《Cell death & disease》2021,12(8)
Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder. Increased Aβ production plays a fundamental role in the pathogenesis of the disease and BACE1, the protease that triggers the amyloidogenic processing of APP, is a key protein and a pharmacological target in AD. Changes in neuronal activity have been linked to BACE1 expression and Aβ generation, but the underlying mechanisms are still unclear. We provide clear evidence for the role of Casein Kinase 2 in the control of activity-driven BACE1 expression in cultured primary neurons, organotypic brain slices, and murine AD models. More specifically, we demonstrate that neuronal activity promotes Casein Kinase 2 dependent phosphorylation of the translation initiation factor eIF4B and this, in turn, controls BACE1 expression and APP processing. Finally, we show that eIF4B expression and phosphorylation are increased in the brain of APPPS1 and APP-KI mice, as well as in AD patients. Overall, we provide a definition of a mechanism linking brain activity with amyloid production and deposition, opening new perspectives from the therapeutic standpoint.Subject terms: Kinases, Alzheimer''s disease, Neuronal physiology, Pathogenesis 相似文献
48.
Role of caveolin-1 and cytoskeletal proteins, actin and vimentin, in adipogenesis of bovine intramuscular preadipocyte cells 总被引:6,自引:0,他引:6
We investigated the involvement of caveolin-1 and the cytoskeletal proteins, actin and vimentin, in the adipogenesis of bovine intramuscular preadipocyte (BIP) cells. Immunoblot analysis demonstrated that levels of caveolin-1 and actin gradually increased during adipose conversion in BIP cells, whereas a slight decrease was observed for vimentin. We found that part of the vimentin was clearly distributed to caveolin-1-enriched membrane fractions in BIP cells, but actin was not. During adipogenesis of BIP cells, treatment with the tubulin depolymerizer, nocodazole, significantly increased intracellular triglyceride accumulation compared to non-treated cells. Immunocytochemical analysis showed that actin microfilaments were significantly disrupted in nocodazole-treated cells. Also, a decrease in the localization of vimentin in caveolin-1-enriched fractions and a failure of vimentin to co-immunoisolate with caveolin-1 were observed in nocodazole-treated cells. These results suggest that a rearrangement of cytoskeletal proteins has a role in the intracellular accumulation of lipid droplets during adipogenesis of BIP cells. 相似文献
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【目的】抗反转录病毒疗法(ART)能够有效控制人免疫缺陷病毒(Human immunodeficiency virus-1,HIV-1)的复制,但是不能将其完全清除。至2012年底,全球仍有3 500万HIV-1感染者,同年约160万人死于艾滋病(Acquired immune deficiency syndrome,AIDS)及其相关疾病。HIV-1感染难以根治的主要原因之一是机体内HIV-1潜伏储存库(Reservoir)的存在。HIV-1潜伏储存库主要由CD4+T细胞和单核巨噬细胞构成,与CD4+T细胞相比,目前研究者对单核巨噬系细胞中HIV-1病毒复制机制尚不明了,且缺乏适宜的研究体系。因此,为探讨单核细胞活化或分化信号对HIV-1复制的影响,我们建立了旨在研究HIV-1前病毒转录调控机制的人单核巨噬细胞系模型。【方法】构建env区域移码突变和nef区域携带EGFP或Nano Luc报告基因的HIV-1 NLn GFP-Kp或NLn Nano Luc-Kp重组病毒,分别感染2种人单核细胞系THP-1或U937细胞。通过有限稀释法制备单克隆细胞系,利用流式细胞术或Nano Luc荧光素酶活性分析检测报告基因的表达。筛选EGFP或Nano Luc阴性表达的细胞克隆,经激活剂佛波酯(Phorbol-12-myristate-13-acetate,PMA)刺激后鉴定潜伏感染的细胞克隆。【结果】研究中鉴定了4个HIV-1潜伏感染的细胞克隆。其中2个是表达EGFP的THP-1克隆,2个是以Nano Luc为报告基因的U937克隆。这些克隆在PMA刺激处理后皆有报告基因的表达,而在恒态条件下未检测到报告基因的表达。【结论】成功建立了4个HIV-1潜伏感染的人单核细胞系克隆,该模型有助于理解单核巨噬系细胞的HIV-1病毒复制机制,可能成为进一步研究HIV-1前病毒转录调控机制的有力工具。 相似文献