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   5005篇
  免费   521篇
  国内免费   647篇
  2024年   10篇
  2023年   69篇
  2022年   99篇
  2021年   330篇
  2020年   254篇
  2019年   326篇
  2018年   209篇
  2017年   188篇
  2016年   253篇
  2015年   375篇
  2014年   386篇
  2013年   437篇
  2012年   492篇
  2011年   459篇
  2010年   280篇
  2009年   267篇
  2008年   287篇
  2007年   198篇
  2006年   195篇
  2005年   170篇
  2004年   136篇
  2003年   126篇
  2002年   128篇
  2001年   90篇
  2000年   76篇
  1999年   53篇
  1998年   41篇
  1997年   37篇
  1996年   25篇
  1995年   24篇
  1994年   21篇
  1993年   18篇
  1992年   25篇
  1991年   16篇
  1990年   15篇
  1989年   11篇
  1988年   12篇
  1987年   5篇
  1986年   8篇
  1985年   6篇
  1984年   1篇
  1983年   4篇
  1982年   2篇
  1981年   1篇
  1980年   3篇
  1979年   2篇
  1969年   1篇
  1935年   1篇
  1934年   1篇
排序方式: 共有6173条查询结果,搜索用时 546 毫秒
71.
This work aimed to investigate miR‐93‐5p expression in tumor tissue and its in vitro effects in colorectal cancer (CRC) by targeting programmed death ligand‐1 (PD‐L1). MiR‐93‐5p and PD‐L1 expression was detected in CRC and adjacent normal tissues by quantitative real‐time polymerase chain reaction and immunohistochemistry. The correlation between miR‐93‐5p and PD‐L1 was validated by a dual‐luciferase reporter assay. HCT116 and SW480 cells were divided into blank, miR‐NC, miR‐93‐5p mimics, miR‐93‐5p inhibitor, PD‐L1 small interfering RNA (siRNA) and miR‐93‐5p inhibitor + PD‐L1 siRNA groups, and wound‐healing and transwell assays were performed to detect cell migration and invasion, respectively. Protein expression was measured by western blotting. The secretion of cytokines was detected in the CRC cell/T coculture models. MiR‐93‐5p was downregulated in CRC tissues with upregulated PD‐L1. In PD‐L1‐negative patients, miR‐93‐5p expression was increased compared with that in PD‐L1‐positive patients. MiR‐93‐5p and PD‐L1 expression levels were associated with the tumor differentiation, lymphatic metastasis, TNM, Duke's stage, and prognosis of CRC. PD‐L1 siRNA weakened the migration and invasion abilities via decreased expression of matrix metalloproteinase‐1 (MMP‐1), ‐2, and ‐9, and these effects were abolished by the miR‐93‐5p inhibitor. Additionally, anti‐PD‐L1 upregulated the expressions of interleukin‐2 (IL‐2), tumor necrosis factor‐α (TNF‐α), and interferon γ (IFN‐γ) in the coculture of T cells with CRC cells, but downregulated the expressions of IL‐1β, IL‐10, and TGF‐β. However, these changes were partially reversed by miR‐93‐5p inhibition. miR‐93‐5p is expected to be a novel target for CRC treatment since it decreases the migration and invasion, as well as the immune evasion, of CRC cells via targeting PD‐L1.  相似文献   
72.
Scyllo‐inositol (SI), a stereoisomer of inositol, is regarded as a promising therapeutic agent for Alzheimer's disease. Here, an in vitro cofactor‐balance biotransformation for the production of SI from myo‐inositol (MI) by thermophilic myo‐inositol 2‐dehydrogenase (IDH) and scyllo‐inositol 2‐dehydrogenase (SIDH) is presented. These two enzymes (i.e., IDH and SIDH from Geobacillus kaustophilus) are co‐expressed in Escherichia coli BL21(DE3), and E. coli cells containing the two enzymes are permeabilized by heat treatment as whole‐cell catalysts to convert MI to SI. After condition optimizations about permeabilized temperature, reaction temperature, and initial MI concentration, about 82 g L?1 of SI is produced from 250 g L?1 of MI within 24 h without any cofactor supplementation. This final titer of SI produced is the highest to the authors’ limited knowledge. This study provides a promising method for the large‐scale industrial production of SI.  相似文献   
73.
Fetuses exposed to an inflammatory environment are predisposed to long‐term adverse neurological outcomes. However, the mechanism by which intrauterine inflammation (IUI) is responsible for abnormal fetal brain development is not fully understood. The mechanistic target of rapamycin (mTOR) signaling pathway is closely associated with fetal brain development. We hypothesized that mTOR signaling might be involved in fetal brain injury and malformation when fetuses are exposed to the IUI environment. A well‐established IUI model was utilized by intrauterine injection of lipopolysaccharide (LPS) to explore the effect of IUI on mTOR signaling in mouse fetal brains. We found that microglia activation in LPS fetal brains was increased, as demonstrated by elevated Iba‐1 protein level and immunofluorescence density. LPS fetal brains also showed reduced neuronal cell counts, decreased cell proliferation demonstrated by low Ki67‐positive density, and elevated neuron apoptosis evidenced by high expression of cleaved Caspase 3. Furthermore, we found that mTOR signaling in LPS fetal brains was elevated at 2 hr after LPS treatment, declined at 6 hr and showed overall inhibition at 24 hr. In summary, our study revealed that LPS‐induced IUI leads to increased activation of microglia cells, neuronal damage, and dynamic alterations in mTOR signaling in the mouse fetal brain. Our findings indicate that abnormal changes in mTOR signaling may underlie the development of future neurological complications in offspring exposed to prenatal IUI.  相似文献   
74.
Wetlands Ecology and Management - Little is known about the effect of woody plant expansion on decomposition of root mixtures in grass-dominant temperate wetlands. Here, we collected fine roots...  相似文献   
75.
Understanding the drivers of biodiversity is important for forecasting changes in the distribution of life on earth. However, most studies of biodiversity are limited by uneven sampling effort, with some regions or taxa better sampled than others. Numerous methods have been developed to account for differences in sampling effort, but most methods were developed for systematic surveys in which all study units are sampled using the same design and assemblages are sampled randomly. Databases compiled from multiple sources, such as from the literature, often violate these assumptions because they are composed of studies that vary widely in their goals and methods. Here, we compared the performance of several popular methods for estimating parasite diversity based on a large and widely used parasite database, the Global Mammal Parasite Database (GMPD). We created artificial datasets of host–parasite interactions based on the structure of the GMPD, then used these datasets to evaluate which methods best control for differential sampling effort. We evaluated the precision and bias of seven methods, including species accumulation and nonparametric diversity estimators, compared to analyzing the raw data without controlling for sampling variation. We find that nonparametric estimators, and particularly the Chao2 and second-order jackknife estimators, perform better than other methods. However, these estimators still perform poorly relative to systematic sampling, and effect sizes should be interpreted with caution because they tend to be lower than actual effect sizes. Overall, these estimators are more effective in comparative studies than for producing true estimates of diversity. We make recommendations for future sampling strategies and statistical methods that would improve estimates of global parasite diversity.  相似文献   
76.
77.
78.
Plant diversity has a strong impact on a plethora of ecosystem functions and services, especially ecosystem carbon (C) storage. However, the potential context-dependency of biodiversity effects across ecosystem types, environmental conditions and carbon pools remains largely unknown. In this study, we performed a meta-analysis by collecting data from 95 biodiversity-ecosystem functioning (BEF) studies across 60 sites to explore the effects of plant diversity on different C pools, including aboveground and belowground plant biomass, soil microbial biomass C and soil C content across different ecosystem types. The results showed that ecosystem C storage was significantly enhanced by plant diversity, with stronger effects on aboveground biomass than on soil C content. Moreover, the response magnitudes of ecosystem C storage increased with the level of species richness and experimental duration across all ecosystems. The effects of plant diversity were more pronounced in grasslands than in forests. Furthermore, the effects of plant diversity on belowground plant biomass increased with aridity index in grasslands and forests, suggesting that climate change might modulate biodiversity effects, which are stronger under wetter conditions but weaker under more arid conditions. Taken together, these results provide novel insights into the important role of plant diversity in ecosystem C storage across critical C pools, ecosystem types and environmental contexts.  相似文献   
79.
为了探究外来红树植物拉关木对乡土红树植物的化感作用,该研究观察了不同浓度(0.1、0.3、0.5g·mL~(-1))的拉关木根、叶水浸提液对乡土红树植物桐花树和正红树的胚轴(种子)萌发、幼苗生长及叶片抗氧化酶活性的影响。结果表明:(1)拉关木水浸提液对桐花树种子的成苗率、萌发指数和根长均存在抑制作用,其中对根长的抑制作用随水浸提液浓度的提高而增强。(2)根水浸提液对桐花树幼苗的根长、苗高、生物量等生长指标的影响总体上均表现为低浓度促进,高浓度抑制。(3)拉关木水浸提液对正红树胚轴的萌发率、萌发指数、生长指标均表现为促进作用,且根水浸提液0.1、0.3 g·mL~(-1)处理组的芽长以及根、叶水浸提液0.1、0.3 g·mL~(-1)处理组的生物量显著大于对照组;拉关木水浸提液对正红树幼苗的生物量也表现为促进作用。(4)抗性生理方面,随着拉关木水浸提液浓度的升高,桐花树和正红树幼苗SOD活性降低,正红树幼苗POD活性在根水浸提液0.3 g·mL~(-1)和叶水浸提液0.1 g·mL~(-1)处理组显著高于对照组。以上结果表明,不同乡土植物对拉关木化感作用的敏感性不同,拉关木水浸提液抑制了桐花树的生长,而对正红树的生长则表现出一定程度的促进作用。  相似文献   
80.
目的分析肺炎支原体感染对川崎病的影响及其机制,以期指导临床诊疗。方法回顾性分析2013年8月至2018年8月我科住院的496例川崎病患儿临床资料,其中合并肺炎支原体感染组193例,未合并肺炎支原体感染组303例。应用倾向评分匹配法1∶1校正2组的年龄、性别、是否为不完全型川崎病、是否使用糖皮质激素、丙种球蛋白使用时间、丙种球蛋白使用方法和阿司匹林初始剂量,比较2组患儿的总发热天数、冠状动脉直径、冠状动脉扩张发生率、冠状动脉瘤发生率和丙种球蛋白无反应发生率。结果川崎病合并肺炎支原体感染组男性患儿多,更易发生颈部淋巴结肿大,年龄、中性粒细胞百分比、血沉和低密度脂蛋白高于川崎病未合并肺炎支原体感染组,血钾、血钙、高密度脂蛋白和白蛋白低于川崎病未合并肺炎支原体感染组,差异有统计学意义(均P<0.05)。应用倾向评分匹配法1∶1配对后发现,川崎病合并肺炎支原体感染组患儿总发热时间更长[8(6~10)d vs 7(6~9)d,Z=-2.089,P<0.05),冠状动脉直径值更大[(2.81±0.81)mm vs(2.63±0.45)mm,t=2.532,P<0.05],冠状动脉瘤发生率更高(5.5% vs 1.1%,χ2=5.516,P<0.05)。结论肺炎支原体感染可能引起川崎病患儿脂质代谢及电解质的紊乱,其炎症反应更强,持续时间更长,对冠状动脉损伤更大。  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