首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   2044篇
  免费   135篇
  国内免费   16篇
  2023年   17篇
  2022年   33篇
  2021年   57篇
  2020年   50篇
  2019年   54篇
  2018年   59篇
  2017年   49篇
  2016年   63篇
  2015年   62篇
  2014年   155篇
  2013年   173篇
  2012年   109篇
  2011年   162篇
  2010年   137篇
  2009年   123篇
  2008年   122篇
  2007年   108篇
  2006年   97篇
  2005年   72篇
  2004年   88篇
  2003年   69篇
  2002年   40篇
  2001年   28篇
  2000年   20篇
  1999年   24篇
  1998年   8篇
  1997年   10篇
  1996年   17篇
  1995年   19篇
  1994年   15篇
  1993年   13篇
  1992年   12篇
  1991年   18篇
  1990年   10篇
  1989年   12篇
  1988年   12篇
  1987年   8篇
  1986年   10篇
  1985年   9篇
  1984年   4篇
  1983年   3篇
  1982年   7篇
  1981年   9篇
  1980年   5篇
  1979年   6篇
  1978年   5篇
  1976年   2篇
  1975年   3篇
  1974年   1篇
  1973年   5篇
排序方式: 共有2195条查询结果,搜索用时 15 毫秒
1.
The actin-associated protein palladin has been shown to be involved in differentiation processes in non-muscle tissues. However, but its function in skeletal muscle has rarely been studied. Palladin plays important roles in the regulation of diverse actin-related signaling in a number of cell types. Since intact actin-cytoskeletal remodeling is necessary for myogenesis, in the present study, we pursue to investigate the role of actin-associated palladin in skeletal muscle differentiation. Palladin in C2C12 myoblasts is knocked-down using specific small interfering RNA (siRNA). The results show that down-regulation of palladin decreased migratory activity of mouse skeletal muscle C2C12 myoblasts. Furthermore, the depletion of palladin enhances C2C12 vitality and proliferation. Of note, the loss of palladin promotes C2C12 to express the myosin heavy chain, suggesting that palladin has a role in the modulation of C2C12 differentiation. It is thus proposed that palladin is required for normal C2C12 myogenesis in vitro.  相似文献   
2.
目的:探讨间充质干细胞(MSCs)对趋化因子VEGF的定向迁移能力与其分化状态之间的关系。方法:本实验运用采用Percoll分离法在体外培养并扩增大鼠骨髓来源MSCs,应用抗氧化剂诱导方案诱导MSCs向神经样细胞分化,运用Boyden chamber及Dunn chamber趋化性迁移装置研究了在趋化因子VEGF诱导下不同分化状态的间充质干细胞定向迁移,比较了各分化状态下细胞的迁移速度和迁移效率。结果:Boyden chamber实验结果显示下室加入不同浓度VEGF后,不同状态细胞向同一浓度VEGF迁移的数量不同,不同浓度VEGF诱导同一状态细胞的迁移数量也不同;Dunn chamber的实验结果显示在某一分化阶段(预诱导24小时)的MSCs具有更高的迁移效率。结论:MSCs的分化影响了其向VEGF的定向迁移,也就是说,不同分化状态的MSCs显示出不同的迁移行为。  相似文献   
3.
4.
Based on the efficacy of EHop-016 as an inhibitor of migration and Rac1 activation, a new series of carbazole derivatives has been synthesized. Cytotoxic and anti-migratory effects of these compounds were evaluated in MCF-7 and MDA-MB-231 breast cancer cell lines. Preliminary investigations of their anticancer activity demonstrated that several compounds have moderate antiproliferative effects on cancer cell lines with GI50 values in the range of 13–50?µM. Furthermore, compounds 3b and 11b inhibit migration activity of metastatic cell line MDA-MB-231 by 32% and 34%, respectively. Compound 11b was shown to inhibit activation of the Rho GTPase Rac1 by 55% at 250?nM in both MDA-MB-231 and MDA-MB-435 cell lines. Compared with the IC50 of Rac1 inhibition by lead compound EHop-016 of 1.1?µM, compound 11b demonstrates 4X improved in vitro efficacy.  相似文献   
5.
目的:探讨不同持续性肾脏替代治疗(CRRT)治疗时机对脓毒症合并急性肾功能不全患者的临床疗效及预后的影响。方法:将我院ICU收治的60例脓毒症合并急性肾功能不全患者,按照CRRT治疗时机分为早期组(1-2期,n=30)和晚期组(3期,n=30)。比较两组患者治疗前后不同时点平均动脉压(MAP)、白细胞(WBC)计数、血红蛋白(HB)、血小板(PLT)计数、急性生理学与慢性健康状况(APACHE)Ⅱ评分等临床资料的变化,机械通气时间,肾功能恢复率及28 d病死率等。结果:与早期组比较,晚期组治疗后WBC计数明显升高(P0.05)。治疗后12 h、24 h、72 h,早期组ACHEⅡ评分较晚期组显著降低(P0.05)。与晚期组比较,早期组机械通气时间显著缩短,肾功能恢复明显升高,28d内病死率也明显降低(P0.05)。结论:脓毒症合并急性肾功能不全患者应早期启动CRRT治疗,最佳介入时间是KDIGO-AKI 3期之前,有助于改善患者预后。  相似文献   
6.
Thrombin cleavage alters the function of osteopontin (OPN) by exposing an integrin binding site and releasing a chemotactic C-terminal fragment. Here, we examined thrombin cleavage of OPN in the context of dendritic cell (DC) migration to define its functional domains. Full-length OPN (OPN-FL), thrombin-cleaved N-terminal fragment (OPN-R), thrombin- and carboxypeptidase B2-double-cleaved N-terminal fragment (OPN-L), and C-terminal fragment (OPN-CTF) did not have intrinsic chemotactic activity, but all potentiated CCL21-induced DC migration. OPN-FL possessed the highest potency, whereas OPNRAA-FL had substantially less activity, indicating the importance of RGD. We identified a conserved 168RSKSKKFRR176 sequence on OPN-FL that spans the thrombin cleavage site, and it demonstrated potent pro-chemotactic effects on CCL21-induced DC migration. OPN-FLR168A had reduced activity, and the double mutant OPNRAA-FLR168A had even lower activity, indicating that these functional domains accounted for most of the pro-chemotactic activity of OPN-FL. OPN-CTF also possessed substantial pro-chemotactic activity, which was fully expressed upon thrombin cleavage and its release from the intact protein, because OPN-CTF was substantially more active than OPNRAA-FLR168A containing the OPN-CTF sequence within the intact protein. OPN-R and OPN-L possessed similar potency, indicating that the newly exposed C-terminal SVVYGLR sequence in OPN-R was not involved in the pro-chemotactic effect. OPN-FL and OPN-CTF did not directly bind to the CD44 standard form or CD44v6. In conclusion, thrombin cleavage of OPN disrupts a pro-chemotactic sequence in intact OPN, and its loss of pro-chemotactic activity is compensated by the release of OPN-CTF, which assumes a new conformation and possesses substantial activity in enhancing chemokine-induced migration of DCs.  相似文献   
7.
The Tamang women tea-labouren of Jalpaiguri district show no significant difference in age at menopause among their three «migration status» groups, viz., MO, M1 and M2+. The mean age at menopause is 47.3±4.26 and the median age is 47.68 years. A significant difference occurs between the observed mean age at menopause and 45 years, which is generally taken to be the menopausal age by convention. These Tamang women seem to be similar to other hill women in respect of age at menopause.  相似文献   
8.
本文用LN及含其活性位点序列的合成肽段cYIGSR和RGDS对小鼠EPC细胞与LN的相互作用机制进行研究。结果表明:合成肽段cYIGSR和RGDS能促进EPC粘附并具协同效应。cYIGSR还能促进EPC扩展与次生TGCs迁移。LNA链上RGD和B_1链上YIGSR两个活性位点协同地参与了LN对EPC的粘附、扩展以及次生TGCs的迁移的促进作用。cY R合用不能完全竞争性抑制EPC与LN的结合,说明还有其他作用位点存在。  相似文献   
9.
Chemotactic migration of fibroblasts toward growth factors relies on their capacity to sense minute extracellular gradients and respond to spatially confined receptor-mediated signals. Currently, mechanisms underlying the gradient sensing of fibroblasts remain poorly understood. Using single-particle tracking methodology, we determined that a lysophosphatidic acid (LPA) gradient induces a spatiotemporally restricted decrease in the mobility of LPA receptor 2 (LPA2) on chemotactic fibroblasts. The onset of decreased LPA2 mobility correlates to the spatial recruitment and coupling to LPA2-interacting proteins that anchor the complex to the cytoskeleton. These localized PDZ motif-mediated macromolecular complexes of LPA2 trigger a Ca2+ puff gradient that governs gradient sensing and directional migration in response to LPA. Disruption of the PDZ motif-mediated assembly of the macromolecular complex of LPA2 disorganizes the gradient of Ca2+ puffs, disrupts gradient sensing, and reduces the directional migration of fibroblasts toward LPA. Our findings illustrate that the asymmetric macromolecular complex formation of chemoattractant receptors mediates gradient sensing and provides a new mechanistic basis for models to describe gradient sensing of fibroblasts.  相似文献   
10.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号