全文获取类型
收费全文 | 752篇 |
免费 | 58篇 |
国内免费 | 70篇 |
出版年
2023年 | 13篇 |
2022年 | 18篇 |
2021年 | 52篇 |
2020年 | 25篇 |
2019年 | 22篇 |
2018年 | 26篇 |
2017年 | 32篇 |
2016年 | 38篇 |
2015年 | 34篇 |
2014年 | 58篇 |
2013年 | 56篇 |
2012年 | 55篇 |
2011年 | 68篇 |
2010年 | 40篇 |
2009年 | 28篇 |
2008年 | 37篇 |
2007年 | 33篇 |
2006年 | 22篇 |
2005年 | 27篇 |
2004年 | 17篇 |
2003年 | 19篇 |
2002年 | 34篇 |
2001年 | 9篇 |
2000年 | 19篇 |
1999年 | 11篇 |
1998年 | 9篇 |
1997年 | 7篇 |
1996年 | 8篇 |
1995年 | 9篇 |
1994年 | 8篇 |
1993年 | 3篇 |
1992年 | 8篇 |
1991年 | 1篇 |
1990年 | 7篇 |
1989年 | 4篇 |
1987年 | 5篇 |
1986年 | 1篇 |
1985年 | 5篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1980年 | 2篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有880条查询结果,搜索用时 21 毫秒
41.
Suppressive effect of epigallocatechin‐3‐O‐gallate on endoglin molecular regulation in myocardial fibrosis in vitro and in vivo 下载免费PDF全文
Chiu‐Mei Lin Hang Chang Bao‐Wei Wang Kou‐Gi Shyu 《Journal of cellular and molecular medicine》2016,20(11):2045-2055
Epigallocatechin‐3‐O‐gallate (EGCG), derived from green tea, has been studied extensively because of its diverse physiological and pharmacological properties. This study evaluates the protective effect of EGCG on angiotensin II (Ang II)‐induced endoglin expression in vitro and in vivo. Cardiac fibroblasts (CFs) from the thoracic aorta of adult Wistar rats were cultured and induced with Ang II. Western blotting, Northern blotting, real‐time PCR and promoter activity assay were performed. Ang II increased endoglin expression significantly as compared with control cells. The specific extracellular signal‐regulated kinase inhibitor SP600125 (JNK inhibitor), EGCG (100 μM) and c‐Jun N‐terminal kinase (JNK) siRNA attenuated endoglin proteins following Ang II induction. In addition, pre‐treated Ang II‐induced endoglin with EGCG diminished the binding activity of AP‐1 by electrophoretic mobility shift assay. Moreover, the luciferase assay results revealed that EGCG suppressed the endoglin promoter activity in Ang II‐induced CFs by AP‐1 binding. Finally, EGCG and the JNK inhibitor (SP600125) were found to have attenuated endoglin expression significantly in Ang II‐induced CFs, as determined through confocal microscopy. Following in vivo acute myocardial infarction (AMI)‐related myocardial fibrosis study, as well as immunohistochemical and confocal analyses, after treatment with endoglin siRNA and EGCG (50 mg/kg), the area of myocardial fibrosis reduced by 53.4% and 64.5% and attenuated the left ventricular end‐diastolic and systolic dimensions, and friction shortening in hemodynamic monitor. In conclusion, epigallocatechin‐3‐O‐gallate (EGCG) attenuated the endoglin expression and myocardial fibrosis by anti‐inflammatory effect in vitro and in vivo, the novel suppressive effect was mediated through JNK/AP‐1 pathway. 相似文献
42.
43.
凝溶胶蛋白(gelsolin,GSN)是Gelsolin/Villin超家族的核心成员,是一种多功能的钙依赖性肌动蛋白结合蛋白,在细胞中Ca^2+和PIP2等多因素的调控下,对细胞凋亡、吞噬功能、肌动蛋白微丝切割、细胞信号转导等方面起着重要的作用。近年来,凝溶胶蛋白还被频繁用于相关疾病的预防、诊断与治疗,但其在调控细胞凋亡、炎症等病理生理中的作用机制还存在些许争议。本研究综述了凝溶胶蛋白的结构特点、生物学功能以及对疾病的诊断和治疗,旨在了解凝溶胶蛋白在生物医学及动物科学等领域的应用以及未来凝溶胶蛋白的发展前景。 相似文献
44.
Insect allatotropin upregulates the biosynthesis of juvenile hormones by the corpus allatum. We raised two rabbit antisera against the allatotropin of Manduca sexta (Mas AT) using a synthetic, multiple-antigenic-peptide that contains a branching heptalysine core and eight Mas AT molecules. Both antisera recognized specifically the same neurons in the larval brain, frontal ganglion and terminal abdominal ganglion of M. sexta as previously reported by others. Immunoassay showed reactivity specific to the Mas AT. Very low or nearly no cross-reactivity was found for two Mas AT-like peptides, a myotropin from Locusta migratoria and a Mas AT-like peptide deduced from the DNA sequence of Aedes aegypti, respectively. Immunopositive neurons also were identified in adult Phormia regina, Dacus dorsalis, Oncopeltus fasciatus, and Mythimna loreyi, and in larval M. loreyi, Bombyx mori, and Andraca bipunctata. At 20 pmol per 25 μl incubation medium (i.e. 8x10(-7) M), synthetic Mas AT significantly stimulated in vitro juvenile hormone biosynthesis by the corpus allatum of adult, sugar-fed females of P. regina to 2.64-fold that of controls. Thus, this study provides the first demonstration that at the higher end of the physiological concentration range, the Mas AT has allatotropic effect in vitro to CA of non-lepidopterans. However, in vivo functions of Mas AT and/or Mas AT-like peptide in P. regina remain to be defined. 相似文献
45.
Han ZM Chen DY Li JS Sun QY Wan QH Kou ZH Rao G Lei L Liu ZH Fang SG 《Molecular reproduction and development》2004,67(2):207-214
Adult somatic cell cloned calves were produced by somatic cell nuclear transfer prepared by fusion of cultured ear fibroblast from a Holstein cow into enucleated oocytes of Luxi Yellow cow. In order to determinate the source of mitochondrial DNA of cloned calves, we designed the breed-specific PCR primers by aligning the known D-loop sequences of Bos taurus and analyzed the displacement loop sequences of five live cloned calves by breed-specific primers PCR. The results demonstrated that mtDNA originated from Holstein breed and that from Luxi breed co-exist in all five live calves. 相似文献
46.
Yang CX Han ZM Wen DC Sun QY Zhang KY Zhang LS Wu YQ Kou ZH Chen DY 《Molecular reproduction and development》2003,65(4):396-401
Interspecies cloning may be used as an effective method to conserve highly endangered species and to support the development of non-human primate animal models for studying therapeutic cloning and nuclear-cytoplasm interaction. The use of the monkey model for biomedical research can avoid legal, ethical, and experimental limitations encountered in a clinical situation. We describe in this study the in vitro development of macaca-rabbit embryos produced by fusing macaca fibroblasts with enucleated rabbit oocytes and examine the fate of mitochondrial DNA in these embryos. We show that macaca-rabbit cloned embryos can develop to the blastocyst stage when cultured in vitro in HECM(10) +10% FBS and that mitochondrial DNA derived from donor somatic cells was detectable in cloned embryos throughout preimplantation development. These results suggest that (1) macaca fibroblast nuclei can dedifferentiate in enucleated metaphase II rabbit oocytes; (2) HECM(10) +10% FBS can break through the development block and support the development of macaca-rabbit cloned embryos to blastocysts; and (3) donor-cell-derived mitochondrial DNA is not eliminated until blastocyst stage. 相似文献
47.
48.
49.
Kou R 《Archives of insect biochemistry and physiology》2002,49(4):215-224
The direct effect of acetylcholine on the activation of the corpora allata (CA) was investigated in the adult male loreyi leafworm, Mythimna loreyi. Acetylcholine, in the presence of the choline esterase inhibitor physostigmine (50 microM), elicited a stimulatory effect on juvenile hormone acids (JHAs) release from the CA. Maximum effect was obtained at concentrations of 10 and 50 microM. Repeated administration of 10 microM acetylcholine on the same CA did not elicit similar stimulatory effect. Since JHA release can be significantly activated by carbachol and not by nicotine, this cholinergic effect is likely to belong to the muscarinic type. The effect of acetylcholine was significantly antagonized by gallamine triethiodide (M(2) antagonist) and 4-DAMP (M(3) antagonist), pirenzepine (M(1) antagonist), and tropicamide (M(4) antagonist) were ineffective. It is concluded that in the adult male M. loreyi, the cholinergic regulation of CA is most likely via M(2) and M(3) muscarinic receptors. 相似文献
50.
Gonzalez E Kou R Lin AJ Golan DE Michel T 《The Journal of biological chemistry》2002,277(42):39554-39560
The endothelial isoform of nitric-oxide synthase (eNOS) undergoes a complex pattern of covalent modifications, including acylation with the fatty acids myristate and palmitate as well as phosphorylation on multiple sites. eNOS acylation is a key determinant for the reversible subcellular targeting of the enzyme to plasmalemmal caveolae. We transfected a series of hemagglutinin epitope-tagged eNOS mutant cDNAs deficient in palmitoylation (palm(-)) and/or myristoylation (myr(-)) into bovine aortic endothelial cells; after treatment with the eNOS agonists sphingosine 1-phosphate or vascular endothelial growth factor, the recombinant eNOS was immunoprecipitated using an antibody directed against the epitope tag, and patterns of eNOS phosphorylation were analyzed in immunoblots probed with phosphorylation state-specific eNOS antibodies. The wild-type eNOS underwent agonist-induced phosphorylation at serine 1179 (a putative site for phosphorylation by kinase Akt), but phosphorylation of the myr(-) eNOS at this residue was nearly abrogated; the palm(-) eNOS exhibited an intermediate phenotype. The addition of the CD8 transmembrane domain to the amino terminus of eNOS acylation-deficient mutants rescued the wild-type phenotype of robust agonist-induced serine 1179 phosphorylation. Thus, membrane targeting, but not necessarily acylation, is the critical determinant for agonist-promoted eNOS phosphorylation at serine 1179. In striking contrast to serine 1179, phosphorylation of eNOS at serine 116 was enhanced in the myr(-) eNOS mutant and was markedly attenuated in the CD8-eNOS membrane-targeted fusion protein. We conclude that eNOS targeting differentially affects eNOS phosphorylation at distinct sites in the protein and suggest that the inter-relationships of eNOS acylation and phosphorylation may modulate eNOS localization and activity and thereby influence NO signaling pathways in the vessel wall. 相似文献