全文获取类型
收费全文 | 29397篇 |
免费 | 15803篇 |
国内免费 | 186篇 |
出版年
2023年 | 39篇 |
2022年 | 158篇 |
2021年 | 529篇 |
2020年 | 2259篇 |
2019年 | 3812篇 |
2018年 | 3910篇 |
2017年 | 4163篇 |
2016年 | 4213篇 |
2015年 | 4203篇 |
2014年 | 3910篇 |
2013年 | 4354篇 |
2012年 | 2062篇 |
2011年 | 1746篇 |
2010年 | 3180篇 |
2009年 | 1960篇 |
2008年 | 866篇 |
2007年 | 447篇 |
2006年 | 409篇 |
2005年 | 438篇 |
2004年 | 427篇 |
2003年 | 392篇 |
2002年 | 381篇 |
2001年 | 372篇 |
2000年 | 269篇 |
1999年 | 207篇 |
1998年 | 60篇 |
1997年 | 40篇 |
1996年 | 35篇 |
1995年 | 31篇 |
1994年 | 50篇 |
1993年 | 25篇 |
1992年 | 65篇 |
1991年 | 64篇 |
1990年 | 36篇 |
1989年 | 36篇 |
1988年 | 29篇 |
1987年 | 24篇 |
1986年 | 20篇 |
1985年 | 21篇 |
1983年 | 8篇 |
1982年 | 8篇 |
1981年 | 7篇 |
1980年 | 12篇 |
1979年 | 12篇 |
1978年 | 13篇 |
1977年 | 12篇 |
1976年 | 9篇 |
1975年 | 10篇 |
1974年 | 9篇 |
1969年 | 6篇 |
排序方式: 共有10000条查询结果,搜索用时 359 毫秒
991.
992.
Tien-Huang Lin Hsin-Ho Liu Tsung-Hsun Tsai Chi-Cheng Chen Teng-Fu Hsieh Shang-Sen Lee Yuan-Ju Lee Wen-Chi Chen Chih-Hsin Tang 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1), belongs to the CC chemokine family which is associated with the disease status and outcomes of cancers. Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. However, the effect of CCL2 on human prostate cancer cells is largely unknown. The aim of this study was to examine the role of CCL2 in integrin expression and migratory activity in prostate cancers.Methods
Prostate cancer migration was examined using Transwell, wound healing, and invasion assay. The PKCδ and c-Src phosphorylations were examined by using western blotting. The qPCR was used to examine the mRNA expression of integrins. A transient transfection protocol was used to examine AP-1 activity.Results
Stimulation of prostate cancer cell lines (PC3, DU145, and LNCaP) induced migration and expression of integrin αvβ3. Treatment of cells with αvβ3 antibody or siRNA abolished CCL2-increased cell migration. CCL2-increased migration and integrin expression were diminished by CCR2 but not by CCR4 inhibitors, suggesting that the CCR2 receptor is involved in CCL2-promoted prostate cancer migration. CCL2 activated a signal transduction pathway that includes PKCδ, c-Src, and AP-1. Reagents that inhibit specific components of this pathway each diminished the ability of CCL2 to effect cell migration and integrin expression.Conclusions
Interaction between CCL2 and CCR2 enhances migration of prostate cancer cells through an increase in αvβ3 integrin production.General significance
CCL2 is a critical factor of prostate cancer metastasis. 相似文献993.
994.
Heat stress is one of a wide variety of factors causing liver injury, a small heat shock protein (HSP), HSP32, is induced by heat stress in the liver. But the biological function of HSP32 in this injury is unclear. To investigate the underlying role of HSP32, RT-PCR, immunocytochemical staining and ELISA were applied to confirm the expression of HSP32. And the underlying mechanism in the pathogenesis of hepatic dysfunction following hyperthermic challenge and the possible involvement of oxidative stress to induce oxidative deterioration of liver functions in developing mice were investigated in this study. Caspase-3mRNA expression and caspase-3 activity of heated liver were also analysed. The results showed that liver injury caused by chronic heat stress(39 °C, 1.5 h/day for 6 weeks) was reversible, caspase-3mRNA expression and caspase-3 activity of heat treated mice were increased after the first three weeks of heat exposure (P<0.05) and high expression levels of HSP32 were observed throughout the duration of experiment (P<0.01). A strong correlation exists between heat-induced liver injury and the induction of HSP32, which suggested that the reversibility of liver injury is involved in the induction of HSP32 in the hepatic cells under continuing heat stress. 相似文献
995.
996.
997.
Alba M. Franco‐Pereira Jacobo de Uña‐Álvarez 《Biometrical journal. Biometrische Zeitschrift》2013,55(1):52-67
In this paper, we introduce a new estimator of a percentile residual life function with censored data under a monotonicity constraint. Specifically, it is assumed that the percentile residual life is a decreasing function. This assumption is useful when estimating the percentile residual life of units, which degenerate with age. We establish a law of the iterated logarithm for the proposed estimator, and its ‐equivalence to the unrestricted estimator. The asymptotic normal distribution of the estimator and its strong approximation to a Gaussian process are also established. We investigate the finite sample performance of the monotone estimator in an extensive simulation study. Finally, data from a clinical trial in primary biliary cirrhosis of the liver are analyzed with the proposed methods. One of the conclusions of our work is that the restricted estimator may be much more efficient than the unrestricted one. 相似文献
998.
Bo Wang Lian Li Yuan Liao Jinqing Li Xingjuan Yu Yi Zhang Jing Xu Huilan Rao Shupeng Chen Lanjun Zhang Limin Zheng 《Cancer immunology, immunotherapy : CII》2013,62(10):1575-1585
The proinflammatory cytokine interleukin 17 (IL-17) is considered to play a crucial role in diverse human tumors; however, its role in disease progression remains controversial. This study investigated the cellular source and distribution of IL-17 in esophageal squamous cell carcinoma (ESCC) in situ and determined its prognostic value. Immunohistochemistry, immunofluorescence and immunoelectron microscopy were used to identify IL-17-expressing cells in ESCC tissues, paying particular attention to their anatomic localization. Kaplan–Meier analysis and Cox proportional hazards regression models were applied to estimate overall survival in 215 ESCC patients with long-term follow-up (>10 years). The results showed that mast cells, but not T cells or macrophages, were the predominant cell type expressing IL-17 in ESCC tissues. Unexpectedly, these IL-17+ cells were highly enriched in the muscularis propria rather than the corresponding tumor nest (p < 0.0001). The density of IL-17+ cells in muscularis propria was inversely associated with tumor invasion (p = 0.016) and served as an independent predictor of favorable survival (p = 0.007). Moreover, the levels of IL-17+ cells in muscularis propria were positively associated with the density of effector CD8+ T cells and activated macrophages in the same area (both p < 0.0001). This finding suggested that mast cells may play a significant role in tumor immunity by releasing IL-17 at a previously unappreciated location, the muscularis propria, in ESCC tissues, which could serve as a potential prognostic marker and a novel therapeutic target for ESCC. 相似文献
999.
Yi Huang Jianqing Zhou Huadan Ye Limin Xu Yanping Le Xi Yang Weifeng Xu Xiaoyan Huang Jiangfang Lian Shiwei Duan 《Gene》2013
The goal of our study is to evaluate the contribution of CXCL12 rs1746048 (hg19, chr10:44775574) to the risk of CHD in Han Chinese, and to summarize its role in CHD through meta-analysis of existing studies among various ethnic groups. Significant association is observed between rs1746048-C and an increased risk of CHD in Han Chinese (χ2 = 5.41, df = 1, P = 0.02). Post hoc analysis reveals an even stronger association of rs1746048 with the risk of CHD for subjects aged 65 years or older (genotype: χ2 = 8.39, df = 2, P = 0.015; allele: χ2 = 9.13, df = 1, P = 0.003, odd ratio (OR) = 1.91, 95% confidential interval (CI) = 1.25–2.91). A break down analysis by gender shows that rs1746048 is likely a CHD risk factor under the recessive model in males (CC + CT versus TT: P = 0.05, χ2 = 3.59, df = 1, OR = 1.72, 95% CI = 1.00–3.04). In addition, a meta-analysis of ten studies among over 107,000 individuals confirms that rs1746048 is a risk factor of CHD (P < 0.0001, OR = 1.12, 95% CI = 1.09–1.15) and this agrees with the findings of our case–control study in Han Chinese. 相似文献
1000.
Yohsuke Ohba Eriko Kage‐Nakadai Naoko H Tomioka Nozomu Kono Rieko Imae Asuka Inoue Junken Aoki Naotada Ishihara Shohei Mitani Hiroyuki Arai 《The EMBO journal》2013,32(9):1265-1279
Glycerol‐3‐phosphate acyltransferase (GPAT) is involved in the first step in glycerolipid synthesis and is localized in both the endoplasmic reticulum (ER) and mitochondria. To clarify the functional differences between ER‐GPAT and mitochondrial (Mt)‐GPAT, we generated both GPAT mutants in C. elegans and demonstrated that Mt‐GPAT is essential for mitochondrial fusion. Mutation of Mt‐GPAT caused excessive mitochondrial fragmentation. The defect was rescued by injection of lysophosphatidic acid (LPA), a direct product of GPAT, and by inhibition of LPA acyltransferase, both of which lead to accumulation of LPA in the cells. Mitochondrial fragmentation in Mt‐GPAT mutants was also rescued by inhibition of mitochondrial fission protein DRP‐1 and by overexpression of mitochondrial fusion protein FZO‐1/mitofusin, suggesting that the fusion/fission balance is affected by Mt‐GPAT depletion. Mitochondrial fragmentation was also observed in Mt‐GPAT‐depleted HeLa cells. A mitochondrial fusion assay using HeLa cells revealed that Mt‐GPAT depletion impaired mitochondrial fusion process. We postulate from these results that LPA produced by Mt‐GPAT functions not only as a precursor for glycerolipid synthesis but also as an essential factor of mitochondrial fusion. 相似文献