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   4766篇
  免费   313篇
  国内免费   402篇
  2024年   8篇
  2023年   68篇
  2022年   160篇
  2021年   241篇
  2020年   154篇
  2019年   186篇
  2018年   187篇
  2017年   141篇
  2016年   203篇
  2015年   261篇
  2014年   342篇
  2013年   372篇
  2012年   416篇
  2011年   352篇
  2010年   230篇
  2009年   211篇
  2008年   236篇
  2007年   166篇
  2006年   177篇
  2005年   190篇
  2004年   173篇
  2003年   163篇
  2002年   125篇
  2001年   122篇
  2000年   84篇
  1999年   95篇
  1998年   51篇
  1997年   36篇
  1996年   37篇
  1995年   36篇
  1994年   31篇
  1993年   20篇
  1992年   28篇
  1991年   27篇
  1990年   31篇
  1989年   8篇
  1988年   17篇
  1987年   12篇
  1986年   9篇
  1985年   8篇
  1984年   10篇
  1983年   8篇
  1982年   7篇
  1981年   5篇
  1980年   6篇
  1979年   3篇
  1978年   3篇
  1977年   3篇
  1975年   6篇
  1974年   3篇
排序方式: 共有5481条查询结果,搜索用时 17 毫秒
921.

Background

Early fluid resuscitation is vital to patients with sepsis. However, the choice of fluid has been a hot topic of discussion. The objective of this study was to evaluate whether the use of albumin-containing fluids for resuscitation in patients with sepsis was associated with a decreased mortality rate.

Methods

We systematically searched PubMed, EMBASE and Cochrane library for eligible randomized controlled trials (RCTs) up to March 2014. The selection of eligible studies, assessment of methodological quality, and extraction of all relevant data were conducted by two authors independently.

Results

In total, 15 RCTs were eligible for analysis. After pooling the data, we found there was no significant effect of albumin-containing fluids on mortality in patients with sepsis of any severity (RR: 0.94, 95% CI: 0.87, 1.02 and RD: –0.01, 95% CI: –0.03, 0.01). The results were robust to subgroup analyses, sensitivity analyses and trial sequential analyses.

Conclusion

The present meta-analysis did not demonstrate significant advantage of using albumin-containing fluids for resuscitation in patients with sepsis of any severity. Given the cost-effectiveness of using albumin, crystalloids should be the first choice for fluid resuscitation in septic patients.  相似文献   
922.
Prolonged and excessive glucocorticoids (GC) exposure resulted from Cushing''s syndrome or GC therapy develops central obesity. Moreover, mitochondria are crucial in adipose energy homeostasis. Thus, we tested the hypothesis that mitochondrial dysfunction may contribute to chronic GC exposure-induced epididymal adiposity in the present study. A total of thirty-six 5-week-old male C57BL/6J mice (∼20 g) were administrated with 100 µg/ml corticosterone (CORT) or vehicle through drinking water for 4 weeks. Chronic CORT exposure mildly decreased body weight without altering food and water intake in mice. The epididymal fat accumulation was increased, but adipocyte size was decreased by CORT. CORT also increased plasma CORT, insulin, leptin, and fibroblast growth factor 21 concentrations as measured by RIA or ELISA. Interestingly, CORT increased plasma levels of triacylglycerols and nonesterified fatty acids, and up-regulated the expression of both lipolytic and lipogenic genes as determined by real-time RT-PCR. Furthermore, CORT impaired mitochondrial biogenesis and oxidative function in epididymal WAT. The reactive oxygen species production was increased and the activities of anti-oxidative enzymes were reduced by CORT treatment as well. Taken together, these findings reveal that chronic CORT administration-induced epididymal adiposity is, at least in part, associated with mitochondrial dysfunction in mouse epididymal white adipose tissue.  相似文献   
923.
924.
Inducing tRNA +1 frameshifting to read a quadruplet codon has the potential to incorporate a non-natural amino acid into the polypeptide chain. While this strategy is being considered for genome expansion in biotechnology and bioengineering endeavors, a major limitation is a lack of understanding of where the shift occurs in an elongation cycle of protein synthesis. Here, we use the high-efficiency +1-frameshifting SufB2 tRNA, containing an extra nucleotide in the anticodon loop, to address this question. Physical and kinetic measurements of the ribosome reading frame of SufB2 identify twice exploration of +1 frameshifting in one elongation cycle, with the major fraction making the shift during translocation from the aminoacyl-tRNA binding (A) site to the peptidyl-tRNA binding (P) site and the remaining fraction making the shift within the P site upon occupancy of the A site in the +1-frame. We demonstrate that the twice exploration of +1 frameshifting occurs during active protein synthesis and that each exploration is consistent with ribosomal conformational dynamics that permits changes of the reading frame. This work indicates that the ribosome itself is a determinant of changes of the reading frame and reveals a mechanistic parallel of +1 frameshifting with –1 frameshifting.  相似文献   
925.
氯苯胁迫对蚕豆幼苗生长和细胞分裂的影响   总被引:12,自引:0,他引:12  
研究了1,2,4-三氯苯(TCB)对蚕豆幼苗生长、根尖细胞分裂及染色体畸变的影响.结果表明,随TCB浓度增加和处理时间延长,蚕豆幼苗根长的生长及根尖细胞有丝分裂指数降低甚至停止.TCB诱发蚕豆根尖细胞有丝分裂过程中染色体数目畸变和结构畸变.50-100μg.g^-1TCB胁迫12-24h,蚕豆根尖染色体的主要损伤形式为c-有丝分裂、染色体桥和不均匀排列,其出现百分率达1.0%--10.3%.300μg.g^-1TCB胁迫12-96h,蚕豆根尖细胞中染色体粘连(S)、S+染色体断裂(S+B)、S+染色体环(S+R)、S+染色体不均匀排列(S+A)及S+染色体桥(S+Be)出现的百分率达47.9%--88.9%,各种类型染色体断裂出现的百分率仅为18.1%--29.6%,说明蚕豆根尖细胞染色体畸变分析可作为TCB土壤污染监测的敏感生物监测指标.  相似文献   
926.
Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.Subject terms: Cancer microenvironment, CNS cancer, Cancer therapy  相似文献   
927.
Aims Precipitation pulses and different land use practices (such as grazing) play important roles in regulating soil respiration and carbon balance of semiarid steppe ecosystems in Inner Mongolia. However, the interactive effects of grazing and rain event magnitude on soil respiration of steppe ecosystems are still unknown. We conducted a manipulative experiment with simulated precipitation pulses in Inner Mongolia steppe to study the possible responses of soil respiration to different precipitation pulse sizes and to examine how grazing may affect the responses of soil respiration to precipitation pulses.Methods Six water treatments with different precipitation pulse sizes (0, 5, 10, 25, 50 and 100 mm) were conducted in the ungrazed and grazed sites, respectively. Variation patterns of soil respiration of each treatment were determined continuously after the water addition treatments.Important findings Rapid and substantial increases in soil respiration occurred 1 day after the water treatments in both sites, and the magnitude and duration of the increase in soil respiration depended on pulse size. Significantly positive relationships between the soil respiration and soil moisture in both sites suggested that soil moisture was the most important factor responsible for soil respiration rate during rain pulse events. The ungrazed site maintained significantly higher soil moisture for a longer time, which was the reason that the soil respiration in the ungrazed site was maintained relatively higher rate and longer period than that in the grazed site after a rain event. The significant exponential relationship between soil temperature and soil respiration was found only in the plots with the high water addition treatments (50 and 100 mm). Lower capacity of soil water holding and lower temperature sensitivity of soil respiration in the grazed site indicated that degraded steppe due to grazing might release less CO2 to the atmosphere through soil respiration under future precipitation and temperature scenarios.  相似文献   
928.
为了对味精废水的污染进行全面的评价,针对不同工艺阶段排放的味精废水,采用小麦、白菜和西红柿等作物种子,以污水为环境介质,进行了种子发芽和根伸长的污染暴露实验,并结合污染现场,进行了相应的定量分析.结果表明,在高浓度原味精废母液中, 小麦种子的发芽抑制率和根伸长的抑制率与废水的浓度呈显著正相关.味精废水对3种作物种子的发芽和根伸长的毒性强弱顺序为:西红柿>白菜>小麦西红柿对味精废水毒性响应最为敏感,可以认为是一种较为理想的生物毒性指示作物.味精生产不同工艺阶段所排放的污水对这3种作物种子的发芽半抑制浓度(IC50)为22.0~32432 mg·L-1,对根伸长的半抑制浓度(IC50)为17.3~3320 mg·L-1.  相似文献   
929.
入侵杂草一年蓬的化感作用研究   总被引:36,自引:5,他引:31  
用入侵杂草一年蓬(Erigeron annuus)地上部分的水浸提液对几种经济作物种子进行萌发培养实验,分别测定种子的最终萌发率、根长以及苗高来研究一年蓬是否存在他感作用。结果表明:(1)一年蓬的化感作用是存在的;(2)一年蓬水浸提液在高浓度下对作物种子萌发、根长和苗高均有明显的抑制作用,而在低浓度下则对长梗白菜、番茄的苗高具有促进生长的作用。  相似文献   
930.
老工矿区污染生态问题与今后研究展望   总被引:6,自引:0,他引:6  
周启星 《应用生态学报》2005,16(6):1146-1150
老工矿区的环境污染及其引发的生态问题,已成为当今制约经济与社会可持续发展的世界性技术难题.对老工矿区这一概念的基本定义与范畴仍有争议,本文首先对这一概念从理论上进行了探讨;然后从剖析我国老工矿区现状尤其是其环境污染现实问题的复杂性入手,对老工矿区的区域二次污染这一科学前沿给予了重点关注;在深入阐述老工矿区环境污染问题复杂性与其特点的基础上,建议今后从国家层面上开展老工矿区二次污染发生机理与控制的系统研究,以及从分子生态毒理学角度系统开展有关新型疾病对环境污染响应的研究,是21世纪初环境科学和生态学研究的两大关键科学问题,这无疑是今后我国环境保护战略的重要组成部分.  相似文献   
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