全文获取类型
收费全文 | 57860篇 |
免费 | 4594篇 |
国内免费 | 4502篇 |
专业分类
66956篇 |
出版年
2024年 | 142篇 |
2023年 | 789篇 |
2022年 | 1851篇 |
2021年 | 3044篇 |
2020年 | 2080篇 |
2019年 | 2501篇 |
2018年 | 2344篇 |
2017年 | 1805篇 |
2016年 | 2544篇 |
2015年 | 3627篇 |
2014年 | 4380篇 |
2013年 | 4436篇 |
2012年 | 5286篇 |
2011年 | 4763篇 |
2010年 | 2882篇 |
2009年 | 2598篇 |
2008年 | 2937篇 |
2007年 | 2635篇 |
2006年 | 2261篇 |
2005年 | 1886篇 |
2004年 | 1509篇 |
2003年 | 1420篇 |
2002年 | 1072篇 |
2001年 | 910篇 |
2000年 | 890篇 |
1999年 | 810篇 |
1998年 | 501篇 |
1997年 | 454篇 |
1996年 | 478篇 |
1995年 | 423篇 |
1994年 | 413篇 |
1993年 | 325篇 |
1992年 | 446篇 |
1991年 | 324篇 |
1990年 | 285篇 |
1989年 | 260篇 |
1988年 | 210篇 |
1987年 | 194篇 |
1986年 | 176篇 |
1985年 | 154篇 |
1984年 | 115篇 |
1983年 | 122篇 |
1982年 | 83篇 |
1981年 | 45篇 |
1980年 | 51篇 |
1979年 | 63篇 |
1976年 | 46篇 |
1974年 | 54篇 |
1973年 | 45篇 |
1972年 | 53篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
921.
Interferon regulatory factor-4 binding protein (IBP) is a novel upstream activator of Rho GTPases. Our previous studies have shown that ectopic expression of IBP was correlated with malignant behaviors of human breast cancer cells, and invasive human breast cancer had high expression of IBP that promoted the proliferation of these cells. However, it remains unknown whether autophagy inhibition contributes to IBP-mediated tumorigenesis. In this study, we for the first time, reported that upregulation of IBP expression significantly suppressed the autophagy of breast cancer cells, and downregulation of IBP expression markedly induced autophagy of these cells. Further investigation revealed that IBP effectively counteracted autophagy by directly activating mammalian target of rapamycin complex 2 (mTORC2) and upregulating phosphorylation of Akt on ser473 and FOXO3a on Thr32. Moreover, IBP-mediated suppression of autophagy was dependent on mTORC2/Akt/FOXO3a signaling pathway. Finally, our results demonstrated that IBP-mediated breast cancer cell growth in vitro and in vivo was strongly correlated with suppression of mTORC2-dependent autophagy. These findings suggest that the anti-autophagic property of IBP has an important role in IBP-mediated tumorigenesis, and IBP may serve as an attractive target for treatment of breast cancer. 相似文献
922.
Jianjian Shi Xiangbing Wu Michelle Surma Sasidhar Vemula Lumin Zhang Yu Yang Reuben Kapur Lei Wei 《Cell death & disease》2013,4(2):e483
This study, using mouse embryonic fibroblast (MEF) cells derived from ROCK1−/− and ROCK2−/− mice, is designed to dissect roles for ROCK1 and ROCK2 in regulating actin cytoskeleton reorganization induced by doxorubicin, a chemotherapeutic drug. ROCK1−/− MEFs exhibited improved actin cytoskeleton stability characterized by attenuated periphery actomyosin ring formation and preserved central stress fibers, associated with decreased myosin light chain 2 (MLC2) phosphorylation but preserved cofilin phosphorylation. These effects resulted in a significant reduction in cell shrinkage, detachment, and predetachment apoptosis. In contrast, ROCK2−/− MEFs showed increased periphery membrane folding and impaired cell adhesion, associated with reduced phosphorylation of both MLC2 and cofilin. Treatment with inhibitor of myosin (blebbistatin), inhibitor of actin polymerization (cytochalasin D), and ROCK pan-inhibitor (Y27632) confirmed the contributions of actomyosin contraction and stress fiber instability to stress-induced actin cytoskeleton reorganization. These results support a novel concept that ROCK1 is involved in destabilizing actin cytoskeleton through regulating MLC2 phosphorylation and peripheral actomyosin contraction, whereas ROCK2 is required for stabilizing actin cytoskeleton through regulating cofilin phosphorylation. Consequently, ROCK1 and ROCK2 can be functional different in regulating stress-induced stress fiber disassembly and cell detachment. 相似文献
923.
Juan Lin Hanjie Li Min Yang Junming Ren Zhe Huang Felicia Han Jian Huang Jianhui Ma Duanwu Zhang Zhirong Zhang Jianfeng Wu Deli Huang Muzhen Qiao Guanghui Jin Qiao Wu Yinghui Huang Jie Du Jiahuai Han 《Cell reports》2013,3(1):200-210
Highlights? RIP3 deficiency in macrophages reduces advanced atherosclerotic lesions ? RIP3 deficiency reduces primary necrosis of macrophages in advanced lesions ? RIP3-dependent macrophage necrosis is not postapoptotic cell death ? Increased RIP3 converts apoptosis to necrosis in advanced lesional macrophages 相似文献
924.
925.
The clinical use of pluripotent stem cell (PSC)‐derived neural cells requires an efficient differentiation process for mass production in a bioreactor. Toward this goal, neural differentiation of murine embryonic stem cells (ESCs) in three‐dimensional (3D) polyethylene terephthalate microfibrous matrices was investigated in this study. To streamline the process and provide a platform for process integration, the neural differentiation of ESCs was induced with astrocyte‐conditioned medium without the formation of embryoid bodies, starting from undifferentiated ESC aggregates expanded in a suspension bioreactor. The 3D neural differentiation was able to generate a complex neural network in the matrices. When compared to 2D differentiation, 3D differentiation in microfibrous matrices resulted in a higher percentage of nestin‐positive cells (68% vs. 54%) and upregulated gene expressions of nestin, Nurr1, and tyrosine hydroxylase. High purity of neural differentiation in 3D microfibrous matrix was also demonstrated in a spinner bioreactor with 74% nestin + cells. This study demonstrated the feasibility of a scalable process based on 3D differentiation in microfibrous matrices for the production of ESC‐derived neural cells. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:1013–1022, 2013 相似文献
926.
A high efficient Supply Chain (SC) would bring great benefits to an enterprise such as integrated resources, reduced logistics costs, improved logistics efficiency and high quality of overall level of services. So it is important to research various methods, performance indicator systems and technology for evaluating, monitoring, predicting and optimizing the performance of a SC. In this paper, the existing performance indicator systems and methods are discussed and evaluated. Various nature-inspired algorithms are reviewed and their applications for SC Performance Evaluation (PE) are discussed. Then, a model is proposed and developed using 5 Dimensional Balanced Scorecard (5DBSC) and LMBP (Levenberg-Marquardt Back Propagation) neural network for SC PE. A program is written using Matlab tool box to implement the model based on the practical values of the 14 indicators of 5DBSC of a given previous period. This model can be used to evaluate, predict and optimize the performance of a SC. The analysis results of a case study of a company show that the proposed model is valid, reliable and effective. The convergence speed is faster than that in the previous work. 相似文献
927.
Titanium alloy is one of the best materials for biomedical applications due to its superior biocompatibility, outstanding corrosion resistance, and low elastic modulus. However, the friction and wear behaviors of titanium alloys were sensitive to the environment including lubrication. In order to clarify the wear mechanism of titanium alloy under different lubrications including deionized water, physiological saline and bovine serum, the friction and wear tests were performed between Ti6Al4V plates and Si3N4 ball on a universal multi-functional tester. The friction and the wear rate of titanium alloy were measured under dry friction and three different lubrication conditions. The worn surfaces were examined by scanning electron microscopy. The results revealed that under the dry friction, the wear resistance of titanium alloy was the worst since the wear mechanism was mainly the combination of abrasive wear and oxidation wear. It was also found that Ti6Al4V alloy had low friction coefficient and wear rate under three lubrication conditions, and its wear mechanism was adhesive wear. 相似文献
928.
929.
Aixia Li Wenlong Yang Xueyuan Lou Dongcheng Liu Jiazhu Sun Xiaoli Guo Jing Wang Yiwen Li Kehui Zhan Hong-Qing Ling Aimin Zhang 《植物学报(英文版)》2013,55(11):1026-1037
Plant height is an important agronomic trait. Dramatic increase in wheat yield during the "green revolution" is mainly due to the widespread utilization of the Reduced height (Rht)-1gene. We analyzed the natural allelic variations of three homoeologous loci Rht-A1, Rht-B1, and Rht-D1 in Chinese wheat (Triticum aestivum L.) micro-core collections and the Rht-B1/D1 genotypes in over 1,500 bred cultivars and germplasms using a modified EcoTILLING. We identified six new Rht-A1 allelic variations (Rht-Alb-g), eight new Rht-B1 allelic variations (Rht-Blh-o), and six new Rht-D1 allelic variations (Rht-Dle-j). These allelic variations contain single nucleotide polymorphisms (SNPs) or small insertions and deletions in the coding or uncoding regions, involving two frame-shift mutations and 15 missenses. Of which, Rht-Dle and Rht-Dlh resulted in the loss of interactions of GID1-DELLA-GID2, Rht-Blicould increase plant height. We found that the Rht-Blh contains the same SNPs and 197 bp fragment insertion as reported in Rht-Blc. Further detection of Rht-Blh in Tibet wheat germplasms and wheat relatives indicated that Rht-Blc may originate from Rht-Blh. These results suggest rich genetic diversity at the Rht-1 loci and provide new resources for wheat breeding. 相似文献
930.
Xiao-Chen Chen Hao Sun Chang-Jun Zhang Ying Zhang Ke-Qin Lin Liang Yu Lei Shi Yu-Fen Tao Xiao-Qin Huang Jia-You Chu Zhao-Qing Yang 《遗传学报》2013,40(10):543-548
The ataxin-2 (ATXN2) gene is located on human chromo-some 12q24.1. In normal individuals, the coding region in exon 1 of this gene has fewer than 31 CAG repeats (Yu et al., 2005: Laffita-Mesa et al., 2012). However, an abnormal expansion of CAG trinucleotide repeats results in the aggre-gation of polyglutamine (polyQ), which causes spinocer-ebellar ataxia type 2 (SCA2) (Pulst et al., 1996). The expanded alleles have more than 32 repeats in the affected individuals, and generally there is an inverse correlation between CAG repeat length and age of onset (Pulst et al., 1996). SCA2 is an autosomal dominant inheritance neurodegenerative disease, whose major clinical feature is progressive cerebellar ataxia. Atrophies of the brainstem and frontal lobe have been frequently detected by magnetic resonance imaging (MRI) (Yamamoto-Watanabe et al., 2010). This disease has the strong effect on sensory and motor control. 相似文献