全文获取类型
收费全文 | 2307篇 |
免费 | 214篇 |
国内免费 | 159篇 |
专业分类
2680篇 |
出版年
2024年 | 3篇 |
2023年 | 23篇 |
2022年 | 78篇 |
2021年 | 114篇 |
2020年 | 83篇 |
2019年 | 95篇 |
2018年 | 110篇 |
2017年 | 79篇 |
2016年 | 125篇 |
2015年 | 163篇 |
2014年 | 151篇 |
2013年 | 180篇 |
2012年 | 208篇 |
2011年 | 179篇 |
2010年 | 108篇 |
2009年 | 78篇 |
2008年 | 117篇 |
2007年 | 108篇 |
2006年 | 82篇 |
2005年 | 82篇 |
2004年 | 61篇 |
2003年 | 60篇 |
2002年 | 48篇 |
2001年 | 44篇 |
2000年 | 38篇 |
1999年 | 36篇 |
1998年 | 26篇 |
1997年 | 25篇 |
1996年 | 29篇 |
1995年 | 22篇 |
1994年 | 16篇 |
1993年 | 12篇 |
1992年 | 13篇 |
1991年 | 10篇 |
1990年 | 13篇 |
1989年 | 5篇 |
1988年 | 7篇 |
1987年 | 13篇 |
1986年 | 6篇 |
1985年 | 7篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1971年 | 2篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有2680条查询结果,搜索用时 0 毫秒
51.
52.
Bi Song Alexandra M. Smink Christina V. Jones Judy M. Callaghan Stephen D. Firth Claude A. Bernard Andrew L. Laslett Peter G. Kerr Sharon D. Ricardo 《PloS one》2012,7(9)
The loss of glomerular podocytes is a key event in the progression of chronic kidney disease resulting in proteinuria and declining function. Podocytes are slow cycling cells that are considered terminally differentiated. Here we provide the first report of the directed differentiation of induced pluripotent stem (iPS) cells to generate kidney cells with podocyte features. The iPS-derived podocytes share a morphological phenotype analogous with cultured human podocytes. Following 10 days of directed differentiation, iPS podocytes had an up-regulated expression of mRNA and protein localization for podocyte markers including synaptopodin, nephrin and Wilm’s tumour protein (WT1), combined with a down-regulation of the stem cell marker OCT3/4. In contrast to human podocytes that become quiescent in culture, iPS-derived cells maintain a proliferative capacity suggestive of a more immature phenotype. The transduction of iPS podocytes with fluorescent labeled-talin that were immunostained with podocin showed a cytoplasmic contractile response to angiotensin II (AII). A permeability assay provided functional evidence of albumin uptake in the cytoplasm of iPS podocytes comparable to human podocytes. Moreover, labeled iPS-derived podocytes were found to integrate into reaggregated metanephric kidney explants where they incorporated into developing glomeruli and co-expressed WT1. This study establishes the differentiation of iPS cells to kidney podocytes that will be useful for screening new treatments, understanding podocyte pathogenesis, and offering possibilities for regenerative medicine. 相似文献
53.
Jingdan Xie Qian Bi Wen li Wen Shang Ming Yan Yebing Yang Danmin Miao Huiming Zhang 《PloS one》2012,7(10)
Background
The relationship between anxiety and depression in pain patients has not been clarified comprehensively. Previous research has identified a common factor in anxiety and depression, which may explain why depression and anxiety are strongly correlated. However, the specific clinical features of anxiety and depression seem to pull in opposite directions.Objective
The purpose of this study is to develop a statistical model of depression and anxiety, based on data from pain patients using Hospital Anxiety and Depression Scale (HADS). This model should account for the positive correlation between depression and anxiety in terms of a general factor and also demonstrate a latent negative correlation between the specific factors underlying depression and anxiety.Methods
The anxiety and depression symptoms of pain patients were evaluated using the HADS and the severity of their pain was assessed with the visual analogue scale (VAS). We developed a hierarchical model of the data using an IRT method called bifactor analysis. In addition, we tested this hierarchical model with model fit comparisons with unidimensional, bidimensional, and tridimensional models. The correlations among anxiety, depression, and pain severity were compared, based on both the bidimensional model and our hierarchical model.Results
The bidimensional model analysis found that there was a large positive correlation between anxiety and depression (r = 0.638), and both scores were significantly positively correlated with pain severity. After extracting general factor of distress using bifactor analysis, the specific factors underlying anxiety and depression were weakly but significantly negatively correlated (r = −0.245) and only the general factor was significantly correlated with pain severity. Compared with the three first-order models, the bifactor hierarchical model had the best model fit.Conclusion
Our results support the hypothesis that apart from distress, anxiety and depression are inversely correlated. This finding has not been convincingly demonstrated in previous research. 相似文献54.
Yimin Dai Qingfeng Zhou Chengwen Zhang Yanhua Song Xiaoyan Tian Xiangbin Zhang Chunyi Xue Shun Xu Yingzuo Bi Yongchang Cao 《Journal of virology》2012,86(22):12456
Porcine orthoreoviruses belong to the family Reoviridae and cause mainly mild enteritis in piglets. We present here the complete genome sequence of a novel porcine orthoreovirus strain (GD-1) isolated from a piglet in southern China. Our data will facilitate future investigations of the molecular characteristics and epidemiology of porcine orthoreoviruses. 相似文献
55.
56.
Elizabeth B. Agnew Richard H. Wilson Jean L. Grem Leonard Neckers Daoqin Bi Chris H. Takimoto 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2001,755(1-2)
A sensitive HPLC assay has been developed to determine the concentration of 17-(allylamino)-17-demethoxygeldanamycin (AAG) in human plasma over the concentration range of 12.5 to 2500 nM (7.33 to 1465 ng/mL). After the addition of 1000 nM geldanamycin as the internal standard, 1 mL samples of human plasma were subjected to solid-phase extraction, via Bond-Elut C18 cartridges, followed by analysis using an isocratic reversed-phase HPLC assay with UV detection. A Phenomenex Kingsorb, 3 micron, C18, 150×4.60 mm column and a Phenomenex Security Guard pre-column, C18 (ODS, Octadecyl), were used to achieve separation. AAG and GM were monitored at 334 and 308 nm, respectively, on a Hewlett-Packard 1050 Diode-Array Detector. The mobile phase, run at a flow-rate of 1 mL/min, was composed of 50% (v/v) 25 mM sodium phosphate (pH 3.00) with 10 mM triethylamine and 50% acetonitrile. HPLC effectively resolved AAG with retention times of 14.60
0.54 min and the internal standard geldanamycin at 10.72±0.38 min (n=15). This assay was able to measure plasma concentrations of AAG, the lower limit of quantitation being 12.5 nM, at a starting dose of 10 mg/m2 infused intravenously over 1 h in a Phase I clinical trial in adult patients with solid tumors. 相似文献
57.
P. Li C. Z. Zhao Y. Q. Zhand X. M. Wang J. F. Wang F. Wang Y. R. Bi 《Biologia Plantarum》2017,61(4):741-750
Silicon (Si) could enhance plant tolerance to heavy metals; however, the mechanism of Si-mediated alleviation of cadmium (Cd) toxicity in Poa annua was not clear. In this study, we found that 100 μM Cd significantly inhibited the growth of Poa annua seedlings. Furthermore, Cd enhanced the H2O2 and malondialdehyde content. The activities of superoxide dismutase and ascorbate peroxidase were enhanced, but the catalase and peroxidase activities were reduced by Cd treatment. Cd also altered the activity and expression of glucose-6-phosphate dehydrogenase (G6PDH) in Poa annua roots. Application of Na3PO4, an inhibitor of G6PDH, decreased the activity of G6PDH, the expression of G6PDH, and increased the Cd toxicity, suggesting that G6PDH is involved in the regulation of oxidative stress induced by Cd. Application of 1 mM Si alleviated the inhibition of Cd on the growth of Poa annua seedlings. Si application not only led to reduced oxidative injuries but also decreased the accumulation of Cd in Poa annua seedlings under Cd stress. Furthermore, Si decreased the activity of G6PDH and the expression of G6PDH under Cd stress, which demonstrated that Si attenuates the Cd toxicity in Poa annua probably through decreasing the expression of G6PDH under Cd stress. When G6PDH was inhibited, the alleviation impact of Si on Cd stress was abolished. Taken together, these results demonstrated that the Cd tolerance in Poa annua enhanced by Si is mainly due to the decrease of Cd uptake in roots and lowering the oxidative stress induced by Cd. 相似文献
58.
Spectroscopic and in silico study of binding mechanism of cynidine‐3‐O‐glucoside with human serum albumin and glycated human serum albumin 下载免费PDF全文
The drug–serum albumin interaction plays a dominant role in drug efficacy and disposition. The glycation of serum albumin that occurs during diabetes may affect its drug‐binding properties in vivo. In order to evaluate the interactivity characteristics of cyanidin‐3‐O‐glucoside (C3G) with human serum albumin (HSA) and glycated human serum albumin (gHSA), this study was undertaken using multiple spectroscopic techniques and molecular modeling analysis. Time‐resolved fluorescence and the thermodynamic parameters indicated that the quenching mechanism was static quenching, and hydrogen bonding and Van der Waals force were the main forces. The protein fluorescence could be quenched by C3G, whereas the polarity of the fluorophore was not obviously changed. C3G significantly altered the secondary structure of the proteins. Furthermore, the interaction force that existed in the HSA–C3G system was greater than that in the gHSA–C3G system. Fluorescence excitation emission matrix spectra, red edge excitation shift, Fourier transform infrared spectroscopy and circular dichroism spectra provided further evidence that glycation could inhibit the binding between C3G and proteins. In addition, molecular modeling analysis supported the experimental results. The results provided more details for the application of C3G in the treatment of diabetes. 相似文献
59.
丙型肝炎病毒基因组部份NS5区蛋白基因在大肠杆菌中的表达 总被引:1,自引:0,他引:1
在大肠杆菌中表达了丙型肝炎病毒基因组NS5区A段和部份B段蛋白。NS5A蛋白溶于水,可经过GST亲和层析柱纯化;NS5B蛋白不溶于水,经PBS-Triton X-100洗涤,尿素溶解后,通过离子交换柱纯化。经SDS-PAGE和Westemblot分析,NS5A蛋白除在57kD左右有条带外,还有不同程度的降解产物;NS5B蛋白主要在58kD左右有条带出现。为查明表达蛋白抗体在病人血清中的分布,取9 相似文献
60.