全文获取类型
收费全文 | 394篇 |
免费 | 53篇 |
国内免费 | 78篇 |
出版年
2024年 | 2篇 |
2023年 | 3篇 |
2022年 | 11篇 |
2021年 | 18篇 |
2020年 | 11篇 |
2019年 | 3篇 |
2018年 | 6篇 |
2017年 | 9篇 |
2016年 | 20篇 |
2015年 | 22篇 |
2014年 | 31篇 |
2013年 | 23篇 |
2012年 | 41篇 |
2011年 | 37篇 |
2010年 | 31篇 |
2009年 | 29篇 |
2008年 | 30篇 |
2007年 | 40篇 |
2006年 | 21篇 |
2005年 | 17篇 |
2004年 | 16篇 |
2003年 | 13篇 |
2002年 | 14篇 |
2001年 | 3篇 |
2000年 | 10篇 |
1999年 | 4篇 |
1998年 | 4篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1974年 | 7篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1961年 | 1篇 |
排序方式: 共有525条查询结果,搜索用时 515 毫秒
51.
52.
Activated protein C mediates novel lung endothelial barrier enhancement: role of sphingosine 1-phosphate receptor transactivation 总被引:17,自引:0,他引:17
Finigan JH Dudek SM Singleton PA Chiang ET Jacobson JR Camp SM Ye SQ Garcia JG 《The Journal of biological chemistry》2005,280(17):17286-17293
Increased endothelial cell (EC) permeability is central to the pathophysiology of inflammatory syndromes such as sepsis and acute lung injury (ALI). Activated protein C (APC), a serine protease critically involved in the regulation of coagulation and inflammatory processes, improves sepsis survival through an unknown mechanism. We hypothesized a direct effect of APC to both prevent increased EC permeability and to restore vascular integrity after edemagenic agonists. We measured changes in transendothelial electrical resistance (TER) and observed that APC produced concentration-dependent attenuation of TER reductions evoked by thrombin. We next explored known EC barrier-protective signaling pathways and observed dose-dependent APC-mediated increases in cortical myosin light chain (MLC) phosphorylation in concert with cortically distributed actin polymerization, findings highly suggestive of Rac GTPase involvement. We next determined that APC directly increases Rac1 activity, with inhibition of Rac1 activity significantly attenuating APC-mediated barrier protection to thrombin challenge. Finally, as these signaling events were similar to those evoked by the potent EC barrier-enhancing agonist, sphingosine 1-phosphate (S1P), we explored potential cross-talk between endothelial protein C receptor (EPCR) and S1P1, the receptors for APC and S1P, respectively. EPCR-blocking antibody (RCR-252) significantly attenuated both APC-mediated barrier protection and increased MLC phosphorylation. We next observed rapid, EPCR and PI 3-kinase-dependent, APC-mediated phosphorylation of S1P1 on threonine residues consistent with S1P1 receptor activation. Co-immunoprecipitation studies demonstrate an interaction between EPCR and S1P1 upon APC treatment. Targeted silencing of S1P1 expression using siRNA significantly reduced APC-mediated barrier protection against thrombin. These data suggest that novel EPCR ligation and S1P1 transactivation results in EC cytoskeletal rearrangement and barrier protection, components potentially critical to the improved survival of APC-treated patients with severe sepsis. 相似文献
53.
脂筏是质膜双层中富含鞘脂、胆固醇及特殊蛋白质的质膜微区.对其功能的研究,首先要对其进行分离和鉴定.常利用密度梯度超速离心将其分离,然后以脂筏中富含的神经节苷脂GM1作为标志分子,利用荧光或生物素标记的霍乱毒素-B亚基进行亲和标记来鉴定脂筏.但这一鉴定方法操作复杂、费时、易对环境造成污染,所用关键试剂霍乱毒素不易获得,再加上一些组织GM1含量甚微或不含GM1,使其应用受到局限.为建立一个特异性高又对各种组织广泛适应的脂筏鉴定方法.对两种细胞系脂筏的脂类组分进行了分析.结果发现,可用鞘磷脂作为脂筏的特异性标志分子,采用高效薄层层析技术对脂筏进行鉴定. 相似文献
54.
Vincent Kam Wai Wong Simon Shiu Fai Cheung Ting Li Zhi‐Hong Jiang Jing‐Rong Wang Hang Dong Xiao Qin Yi Hua Zhou Liang Liu 《Journal of cellular biochemistry》2010,111(4):899-910
Asian ginseng (AG) is the most commonly used medicinal herb in Asian countries. It is often prescribed for cancer patients as a complementary remedy. However, whether AG in fact benefits cancer patients remains unknown because some studies reported that AG facilitates tumor growth, which contradicts its usage as a dietary remedy to cancer patients. In addition, most of research works on ginseng for anti‐cancer were using single ginsenoside rather than whole root extracts used in clinics. Thus, intensive studies using the type of ginseng as its clinical form are necessary to validate its benefits to cancer patients. In this study, anti‐tumor potency and underlying molecular mechanisms of the ethanol extract of AG (EAG) were examined in mice with Lewis lung carcinoma (LLC‐1). We showed that EAG significantly suppressed tumor growth in LLC‐1‐bearing mice with concomitant down‐regulation of PCNA proliferative marker, and it exhibited specific cytotoxicity to cancer cells. EAG also induced MAPK and p53 signaling in LLC‐1 cells, which suppressed cyclin B–cdc2 complex and in turn induced G2–M arrest and apoptosis. Although EAG could activate NF‐κB signaling, the proteasome inhibitor of MG‐132 could effectively prevent NF‐κB targeted gene expression induced by EAG and then sensitize LLC‐1 cells to induce EAG‐mediated apoptosis. Collectively, EAG in a relatively high dose significantly suppressed tumor growth in LLC‐1‐bearing mice, indicating that AG may benefit lung cancer patients as a dietary supplement. This is the first report demonstrating possible combination of EAG with proteasome inhibitors could be a novel strategy in anti‐cancer treatment. J. Cell. Biochem. 111: 899–910, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
55.
56.
Hongyi Qi Shiu On Siu Yan Chen Yifan Han Ivan K. Chu Yao Tong Allan S.Y. Lau Jianhui Rong 《Chemico-biological interactions》2010,183(3):380-389
Rhizoma Chuanxiong is widely used as folk medicine to treat the diseases caused by oxidative stress and inflammation. To delineate the underlying molecular mechanisms, we recently found that Rhizoma Chuanxiong extract significantly induced heme oxygenase-1 (HO-1), an enzyme that degrades intracellular heme into three bioactive products: biliverdin, carbon monoxide and free iron. The anti-inflammatory, antiapoptotic and antiproliferative actions of these products highlight HO-1 as a key endogenous antioxidant and cytoprotective gene. This study was designed to further characterize HO-1 induction of Rhizoma Chuanxiong through bioactivity-guided fractionation. All isolated fractions were assayed for HO-1 induction in human HepG2 cell line at mRNA and protein levels. Based on chromatographic profiling, nuclear magnetic resonance (NMR) and mass spectrometric analysis, the active compounds were identified as senkyunolide-H and its stereoisomer senkyunolide-I. Both senkyunolide isomers inhibited the formation of reactive oxygen species and lipid peroxidation and enhanced the cellular resistance to hydrogen peroxide-induced oxidative damage. Notably, heme oxygenase inhibitor tin protoporphyrin IX (SnPP) significantly suppressed the antioxidant activity of senkyunolide stereoisomers. Thus, this study demonstrated that senkyunolide-H and -I attenuated oxidative damage via activation of HO-1 pathway. 相似文献
57.
Yu S Xi Z Hai-Yan C Ya-Li C Shao-Hu X Chuan-Sen Z Xiang-Qun Y Jin-Ping G Hai-Yan L Lei D 《Journal of cellular biochemistry》2012,113(8):2671-2678
High glucose-induced proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development of diabetic vascular diseases. However, molecular mediators responding for the proliferation of VSMCs remain to be determined. In this study, VSMCs were isolated from the rat thoracic aorta, and two cell models with Irf-1 knockdown and overexpression were established by transfecting cells with pGCsi-FU-Irf-1 and pGC-FU-Irf-1, respectively. Subsequently, high glucose was added to cells to induce proliferation. Proliferation assays were performed to see whether Irf-1 was involved in high glucose-induced proliferation of VSMCs. In addition, the expression of Irf-1 was detected in VSMCs stimulated with high glucose and the thoracic aorta of diabetic rats to confirm the relationship between Irf-1 expression and the proliferation of hyperglycemia-dependent VSMCs. The results showed that Irf-1 expression was significantly higher in the thoracic aorta of diabetic rats and VSMCs stimulated with high glucose than that in nondiabetic rats and untreated cells. Overexpression of Irf-1 accelerated the proliferation of VSMCs, and down-regulation of Irf-1 expression significantly depressed the proliferative ability of VSMCs under high-glucose conditions, indicating that Irf-1 was a positive regulator for high glucose-induced proliferation of VSMCs. It could be presumed that Irf-1 is associated with the accelerated proliferation of VSMCs in diabetic vascular diseases and may prove to be a potential target gene for disease treatment. 相似文献
58.
Important photosynthetic contribution from the non-foliar green organs in cotton at the late growth stage 总被引:1,自引:0,他引:1
Non-foliar green organs are recognized as important carbon sources after leaves. However, the contribution of each organ to
total yield has not been comprehensively studied in relation to the time-course of changes in surface area and photosynthetic
activity of different organs at different growth stages. We studied the contribution of leaves, main stem, bracts and capsule
wall in cotton by measuring their time-course of surface area development, O2 evolution capacity and photosynthetic enzyme activity. Because of the early senescence of leaves, non-foliar organs increased
their surface area up to 38.2% of total at late growth stage. Bracts and capsule wall showed less ontogenetic decrease in
O2 evolution capacity per area and photosynthetic enzyme activity than leaves at the late growth stage. The total capacity for
O2 evolution of stalks and bolls (bracts plus capsule wall) was 12.7 and 23.7% (total ca. 36.4%), respectively, as estimated
by multiplying their surface area by their O2 evolution capacity per area. We also kept the bolls (from 15 days after anthesis) or main stem (at the early full bolling
stage) in darkness for comparison with non-darkened controls. Darkening the bolls and main stem reduced the boll weight by
24.1 and 9%, respectively, and the seed weight by 35.9 and 16.3%, respectively. We conclude that non-foliar organs significantly
contribute to the yield at the late growth stage. 相似文献
59.
60.
以马铃薯脱毒试管苗茎段为转化受体材料,建立并优化了农杆菌介导的马铃薯遗传转化体系.通过农杆菌介导法将玉米淀粉分支酶基因(Starch branching enzyme b,SBEⅡb)的过表达载体转化马铃薯,接种762个茎段,共获得35株抗性植株.经PCR检测获得了4株转基因阳性植株;对转基因植株进一步进行GUS活性组织化学染色,发现转基因植株的茎段与试管薯均被染上蓝色,表明外源SBEⅡb基因已整合到马铃薯基因组,且正常表达. 相似文献