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   76238篇
  免费   5553篇
  国内免费   4902篇
  86693篇
  2024年   154篇
  2023年   1039篇
  2022年   2395篇
  2021年   4073篇
  2020年   2622篇
  2019年   3234篇
  2018年   3168篇
  2017年   2299篇
  2016年   3263篇
  2015年   4813篇
  2014年   5548篇
  2013年   5988篇
  2012年   7027篇
  2011年   6170篇
  2010年   3717篇
  2009年   3339篇
  2008年   3733篇
  2007年   3363篇
  2006年   2918篇
  2005年   2390篇
  2004年   1964篇
  2003年   1658篇
  2002年   1401篇
  2001年   1230篇
  2000年   1219篇
  1999年   1122篇
  1998年   661篇
  1997年   655篇
  1996年   666篇
  1995年   618篇
  1994年   544篇
  1993年   376篇
  1992年   569篇
  1991年   435篇
  1990年   406篇
  1989年   282篇
  1988年   244篇
  1987年   234篇
  1986年   166篇
  1985年   193篇
  1984年   109篇
  1983年   117篇
  1982年   71篇
  1981年   58篇
  1980年   37篇
  1979年   61篇
  1977年   30篇
  1974年   38篇
  1973年   34篇
  1972年   30篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
81.
Drug-target interactions provide insight into the drug-side effects and drug repositioning. However, wet-lab biochemical experiments are time-consuming and labor-intensive, and are insufficient to meet the pressing demand for drug research and development. With the rapid advancement of deep learning, computational methods are increasingly applied to screen drug-target interactions. Many methods consider this problem as a binary classification task (binding or not), but ignore the quantitative binding affinity. In this paper, we propose a new end-to-end deep learning method called DeepMHADTA, which uses the multi-head self-attention mechanism in a deep residual network to predict drug-target binding affinity. On two benchmark datasets, our method outperformed several current state-of-the-art methods in terms of multiple performance measures, including mean square error (MSE), consistency index (CI), rm2, and PR curve area (AUPR). The results demonstrated that our method achieved better performance in predicting the drug–target binding affinity.  相似文献   
82.
Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.Subject terms: Cell death, Molecular biology  相似文献   
83.
合成己酸乙酯脂肪酶产生菌的筛选及产酶条件   总被引:5,自引:0,他引:5  
从27株脂肪酶产生菌中筛选到能由乙醇和己酸合成己酸乙酯的菌株8株。其中Rhizopussp.H-3菌株脂肪酶活力为50-60u/ml,全细胞在有机溶剂中的酯化率可达己酸的91%。H3产酶的最适碳源为淀粉或葡萄糖。6%黄豆饼粉加4%蛋白陈复合氮源有利于酶活力的增加。  相似文献   
84.
85.
86.
87.
Deciduous and evergreen trees differ in their responses to drought and nitrogen (N) demand. Whether or not these functional types affect the role of the bacterial community in the N cycle during drought remains uncertain. Two deciduous tree species (Alnus cremastogyne, an N2‐fixing species, and Liquidambar formosana) and two evergreen trees (Cunninghamia lanceolata and Pinus massoniana) were used to assess factors in controlling rhizosphere soil bacterial community and N cycling functions. Photosynthetic rates and biomass production of plants, 16S rRNA sequencing and N‐cycling‐related genes of rhizosphere soil were measured. The relative abundance of the phyla Actinobacteria and Firmicutes was higher, and that of Proteobacteria, Acidobacteria, and Gemmatimondaetes was lower in rhizosphere soil of deciduous trees than that of evergreen. Beta‐diversity of bacterial community also significantly differed between the two types of trees. Deciduous trees showed significantly higher net photosynthetic rates and biomass production than evergreen species both at well water condition and short‐term drought. Root biomass was the most important factor in driving soil bacterial community and N‐cycling functions than total biomass and aboveground biomass. Furthermore, 44 bacteria genera with a decreasing response and 46 taxa showed an increased response along the root biomass gradient. Regarding N‐cycle‐related functional genes, copy numbers of ammonia‐oxidizing bacteria (AOB) and autotrophic ammonia‐oxidizing archaea (AOA), N2 fixation gene (nifH), and denitrification genes (nirK, nirS) were significantly higher in the soil of deciduous trees than in that of the evergreen. Structural equation models explained 50.2%, 47.6%, 48.6%, 49.4%, and 37.3% of the variability in copy numbers of nifH, AOB, AOA, nirK, and nirS, respectively, and revealed that root biomass had significant positive effects on copy numbers of all N‐cycle functional genes. In conclusion, root biomass played key roles in affecting bacterial community structure and soil N cycling. Our findings have important implications for our understanding of plants control over bacterial community and N‐cycling function in artificial forest ecosystems.  相似文献   
88.
89.
Pain is a multidimensional perception that includes unpleasant somatosensory and affective experiences; however, the underlying neural circuits that mediate different components of pain remain elusive. Although hyperactivity of basolateral amygdala glutamatergic (BLAGlu) neurons is required for the somatosensory and emotional processing of pain, the precise excitatory inputs to BLAGlu neurons and their roles in mediating different aspects of pain are unclear. Here, we identified two discrete glutamatergic neuronal circuits in male mice: a projection from the insular cortex glutamatergic (ICGlu) to BLAGlu neurons, which modulates both the somatosensory and affective components of pain, and a projection from the mediodorsal thalamic nucleus (MDGlu) to BLAGlu neurons, which modulates only the aversive-affective component of pain. Using whole-cell recording and fiber photometry, we found that neurons within the IC→BLA and MD→BLA pathways were activated in mice upon inflammatory pain induced by injection of complete Freund’s adjuvant (CFA) into their paws. Optical inhibition of the ICGlu→BLA pathway increased the nociceptive threshold and induced behavioral place preference in CFA mice. In contrast, optical inhibition of the MDGlu→BLA pathway did not affect the nociceptive threshold but still induced place preference in CFA mice. In normal mice, optical activation of the ICGlu→BLA pathway decreased the nociceptive threshold and induced place aversion, while optical activation of the MDGlu→BLA pathway only evoked aversion. Taken together, our results demonstrate that discrete ICGlu→BLA and MDGlu→BLA pathways are involved in modulating different components of pain, provide insights into its circuit basis, and better our understanding of pain perception.  相似文献   
90.
Acute lung injury (ALI) is a potentially life-threatening, devastating disease with an extremely high rate of mortality. The underlying mechanism of ALI is currently unclear. In this study, we aimed to confirm the hub genes associated with ALI and explore their functions and molecular mechanisms using bioinformatics methods. Five microarray datasets available in GEO were used to perform Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs) and the key genes were identified via the protein-protein interaction (PPI) network. Lipopolysaccharide intraperitoneal injection was administered to establish an ALI model. Overall, 40 robust DEGs, which are mainly involved in the inflammatory response, protein catabolic process, and NF-κB signaling pathway were identified. Among these DEGs, we identified two genes associated with ALI, of which the CAV-1/NF-κB axis was significantly upregulated in ALI, and was identified as one of the most effective targets for ALI prevention. Subsequently, the expression of CAV-1 was knocked down using AAV-shCAV-1 or CAV-1-siRNA to study its effect on the pathogenesis of ALI in vivo and in vitro. The results of this study indicated that CAV-1/NF-κB axis levels were elevated in vivo and in vitro, accompanied by an increase in lung inflammation and autophagy. The knockdown of CAV-1 may improve ALI. Mechanistically, inflammation was reduced mainly by decreasing the expression levels of CD3 and F4/80, and activating autophagy by inhibiting AKT/mTOR and promoting the AMPK signaling pathway. Taken together, this study provides crucial evidence that CAV-1 knockdown inhibits the occurrence of ALI, suggesting that the CAV-1/NF-κB axis may be a promising therapeutic target for ALI treatment.Subject terms: Cell signalling, Respiratory tract diseases  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