全文获取类型
收费全文 | 1256篇 |
免费 | 55篇 |
国内免费 | 10篇 |
出版年
2024年 | 2篇 |
2023年 | 9篇 |
2022年 | 21篇 |
2021年 | 28篇 |
2020年 | 57篇 |
2019年 | 58篇 |
2018年 | 50篇 |
2017年 | 39篇 |
2016年 | 37篇 |
2015年 | 47篇 |
2014年 | 115篇 |
2013年 | 108篇 |
2012年 | 83篇 |
2011年 | 92篇 |
2010年 | 49篇 |
2009年 | 49篇 |
2008年 | 70篇 |
2007年 | 69篇 |
2006年 | 55篇 |
2005年 | 38篇 |
2004年 | 53篇 |
2003年 | 44篇 |
2002年 | 32篇 |
2001年 | 10篇 |
2000年 | 14篇 |
1999年 | 9篇 |
1998年 | 5篇 |
1997年 | 7篇 |
1996年 | 9篇 |
1995年 | 7篇 |
1994年 | 6篇 |
1993年 | 4篇 |
1992年 | 5篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有1321条查询结果,搜索用时 250 毫秒
1.
Andrew Leask 《Journal of cell communication and signaling》2010,4(1):71-72
Connective tissue growth factor (CTGF/CCN2) is overexpressed in diabetes. Diabetic rats possess myocardial and cardiomyocyte
hypertrophy. In a recent report, Wang and colleagues (Am J Physiol Cell Physiol. 2009 Jul 22. [Epub ahead of print]) show
that CCN2 directly mediates cardiomyocyte hypertrophy as well as that induced by high glucose and fatty acid. CCN2 acted via
the TrkA receptor. These data are the subject of this commentary, and emphasize that CCN2 may be an excellent target for therapy
in diabetes. 相似文献
2.
《基因组蛋白质组与生物信息学报(英文版)》2020,18(2):104-119
To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to generate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000. 相似文献
3.
Docetaxel resistance remains one of the main problems in clinical treatment of metastatic prostate cancer (PCa). Previous studies identified differently expressed lncRNAs in docetaxel-resistant PCa cell lines, while the potential mechanisms were still unknown. In the present study, we found NEAT1 was expressed at high levels in docetaxel-resistant PCa clinical samples and related cell lines. When knockdown NEAT1, cell proliferation and invasion in docetaxel-resistant PCa cells in vitro and in vivo were downregulated. Our further researches explained that NEAT1 exerts oncogenic function in PCa by competitively ‘sponging’ both miR-34a-5p and miR-204-5p. Inhibition of miR-34a-5p or miR-204-5p expression mimics the docetaxel-resistant activity of NEAT1, whereas ectopic expression of miR-34a-5p or miR-204-5p attenuates the anti-drug function of NEAT1 in PCa cells. Besides, we also found ACSL4 is a target of both miR-34a-5p and miR-204-5p, and ACSL4 was also inhibited by miR-34a-5p and miR-204-5p. Moreover, suppression of miR-34a-5p or/and miR-204-5p greatly restrained the expression of ACSL4 upon NEAT1 overexpression. Joint expression of miR-34a-5p and miR-204a-5p synergistically decreased the expression of ASCL4, indicating miR-34a-5p and miR-204a-5p collaboratively inhibit the expression of ACSL4. Innovatively, we concluded that NEAT1 contributes to the docetaxel resistance by increasing ACSL4 via sponging miR-34a-5p and miR-204-5p in PCa cells. 相似文献
4.
Ali Arslan Cuillermina Almazan Hans H. Zingg 《In vitro cellular & developmental biology. Animal》1995,31(2):140-148
Summary Normal and neoplastic growth of epithelial cells depends on mutual interactions between epithelial and stromal cells. As a
tool for the study of the underlying molecular mechanisms, we have developed temperature-sensitive, nontransformed cell lines
derived from rat uterine epithelium and stroma by transfecting primary cultures with a temperature-sensitive mutant of the
SV40 large T antigen. The epithelial and stromal cell lines obtained shared relevant morphological characteristics with the
primary cells from which they were derived. Immunocytochemical analysis showed that the epithelial cell lines expressed the
intermediate filament cytokeratin, whereas the stromal lines expressed the intermediate filament vimentin. Alkaline phosphatase
activity was present in all cell lines examined. All cell lines were anchorage dependent and did not form foci. One epithelial
cell line expressed oxytocin mRNA, a gene product recently shown to be highly expressed in vivo in the uterine epithelium
at term. If grown on Matrigel, this cell line formed domelike structures, a further characteristic of its differentiated phenotype.
In an attempt to reconstitute an endometrium in vitro, epithelial cells were seeded on top of a layer of stromal cells. Paraffin
cross sections showed that this in vitro system consisted of a bilayer structure. Four to five cuboidal epithelial cells were
typically anchored atop one stromal cell, forming an endometriumlike tissue. The present in vitro system should provide a
useful model for further studies on endometrial functions and epithelial/stromal cell interactions at a molecular level. 相似文献
5.
We produced three monoclonal antibodies, SG1, SG2 and SG3, specific for human seminal -glutamyltransferase when characterized by enzyme-linked immunosorbent assay and immunoblotting. Seminal -glutamyltransferase was localized, by immunostaining, to the epithelial cells of the ductus epididymidis, seminal vesicle and prostate gland with SG1, those of the prostate gland with SG2, and those of the seminal vesicle with SG3. Rabbit polyclonal anti-seminal -glutamyltransferase serum reacted with the proximal convolution of the kidney and the bile capillaries of the liver, and with the epithelial cells of the reproductive organs. However, immunoreactivity was not observed in the kidney or liver with the monoclonal antibodies. Thus, these monoclonal antibodies are probably all specific to seminal -glutamyltransferase but recognize different epitopes. 相似文献
6.
本文应用反义RNA探针原位杂交法,研究雄激素对大鼠腹侧前列腺(VP)上皮细胞角蛋白(CK)8 mRNA表达的影响。发现1.在任何VP组织切片中,CK 8探针专一、大量定位于VP腺上皮细胞中,CK 8 mRNA是前列腺上皮细胞特异而灵敏的标志。2.去睾大鼠VP CK 8 mRNA染色增强,提示CK 8mRNA有过度表达,注射雄激素又可抑制其过度表达。3.与已知受雄激素抑制性基因不同,即使大鼠VP完全萎缩之后达2个月之久,其存留腺上皮细胞CK 8 mRNA表达仍持续增高。4.前列腺发育早期,迅速增殖的幼稚腺上皮细胞高度表达CK 8 mRNA,以后随着体内雄激素水平升高,VP上皮CK 8 mRNA表达下降,分布转移。以上结果进一步支持前列腺CK 8基因是新的一类受雄激素抑制性基因的推测,同时表明前列腺CK 8基因的表达与前列腺干细胞的增殖分化有密切联系,CK 8 mRNA高度表达是前列腺干细胞一个重要特征。 相似文献
7.
Human papilloma virus E6/E7 genes can expand the lifespan of human corneal fibroblasts 总被引:2,自引:0,他引:2
Donna M. Peters Nathan Dowd Curtis Brandt Teresa Compton 《In vitro cellular & developmental biology. Animal》1996,32(5):279-284
Summary Human corneal fibroblasts were infected with a retroviral delivery vector containing the E6 and E7 genes from human Papilloma
virus type 16 in order to produce cell lines that have an expanded lifespan in culture. Morphologically, some of the trasfected
corneal fibroblast lines appeared to have the normal spindle-shape morphology of diploid fibroblasts, whereas other lines
appeared to have a more elongated morphology. All the cell lines were anchorage-dependent. Cells that had a normal morphology
grew at a rate similar to normal diploid human corneal fibroblasts and had a population doubling time of 48 h. All E6/E7 expressing
cell lines, regardless of morphology, produce types I, III, and V collagen, at levels similar to those observed in the parent
corneal diploid fibroblast. These corneal fibroblast lines will be a usefulin vitro system to study collagen expression and fibril formation, as well as normal stroma development. These results also demonstrate
that the use of E6/E7 genes to expand a cell’s lifespan can be a powerful tool because it does not appear to alter either
the growth rate of the cell or collagen expression. 相似文献
8.
从人良性增生前列腺组织中经硫酸铵沉淀和肝素-琼脂糖凝胶层析纯化出人前列腺生长因子(hPGF),纯化倍数约1000倍,SDS-PAGE和等电聚焦电泳示分子量约为17kD、等电点同标准bFGF,利用分离培养的人前列腺间质成纤维细胞进行活性鉴定,发现以1.3~1.7mol/LNaCl洗脱部分为hPGF,活性最高,对间质成纤维细胞有显著刺激增殖作用。 相似文献
9.
François Boutignon Hélène Touchet Sandrine David Patrick Wüthrich Romano Deghenghi Huy Ong Mélanie Dubuc Marina Cesana Tony Maggi 《Letters in Peptide Science》1997,4(4-6):423-427
Avorelin is a new superagonist of naturalluteinizing-hormone-releasing-hormone. Avorelin hasbeen formulated in high molecular weight polylactic glycolic acid to afford protracted andcontinuous release of the peptide from subcutaneousimplants. Two different formulations (10 and 15 mg)were tested first in dogs and then in men during aclinical phase II trial. Chemical castration wasmaintained for at least 6 months in dogs withboth formulations. A similar duration of activity(approximately 6 months) was observed in men. 相似文献
10.
J. A. Chandler F. Sinowatz B. G. Timms C. G. Pierrepoint 《Cell and tissue research》1977,185(1):89-103
Summary X-ray microanalysis of zinc in ultrathin sections of dog prostate was performed by electron microscope microanalysis using the potassium pyroantimonate method of preparation. Prostates of both mature and immature dogs were examined and the metal was found to be localised primarily in the nucleolus, nuclear chromatin and secretory granules of epithelial cells. Differences in zinc concentrations were observed between mature and immature tissues, particularly in the nuclear chromatin. The metal was also incorporated into epithelial secretions, lysosomes and fibromuscular stroma. Variable binding of zinc to tissue components was revealed by a combination of histochemical precipitation and subcellular analysis.The authors are grateful to the Tenovus Organisation for general financial support. This work was also supported by the Medical Research Council, Grant No. G974/304B and by a grant of the Austrian Bundesministerium für Wissenschaft und Forschung. One of them (F.S.) was financed by the British Council 相似文献