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   973篇
  免费   131篇
  国内免费   73篇
  2024年   1篇
  2023年   8篇
  2022年   9篇
  2021年   39篇
  2020年   33篇
  2019年   39篇
  2018年   38篇
  2017年   40篇
  2016年   48篇
  2015年   62篇
  2014年   67篇
  2013年   66篇
  2012年   97篇
  2011年   80篇
  2010年   46篇
  2009年   48篇
  2008年   46篇
  2007年   26篇
  2006年   44篇
  2005年   34篇
  2004年   38篇
  2003年   49篇
  2002年   32篇
  2001年   35篇
  2000年   25篇
  1999年   25篇
  1998年   13篇
  1997年   10篇
  1996年   11篇
  1995年   9篇
  1994年   4篇
  1993年   8篇
  1992年   14篇
  1991年   7篇
  1990年   5篇
  1989年   1篇
  1988年   5篇
  1987年   6篇
  1986年   1篇
  1985年   3篇
  1984年   2篇
  1983年   1篇
  1982年   2篇
排序方式: 共有1177条查询结果,搜索用时 62 毫秒
21.
22.
Maltol is a flavor additive that is widely used in the daily diet of humans, and its biosafety attention is concomitantly increasing. Catalase (CAT) is an antioxidant enzyme to maintain homeostasis in the tissue's environment of human body and protect cells from oxidative damages. The adverse effects of maltol to CAT activity within mouse hepatocytes as well as the structural and functional changes of CAT on molecular level were investigated by multiple spectroscopy techniques, enzyme activity experiments, and molecular docking. Results suggested that when the maltol concentrations reached to 8 × 10?5 mol L?1, the viability of hepatocytes decreased to 93%, and CAT activity was stimulated by maltol to 111% than the control group after exposure for 24 hours. Changes in CAT activity on molecular level were consistent with those on cellular level. The fluorescence quenching of CAT by maltol was static with the forming of maltol‐CAT complex. Moreover, ultraviolet‐visible (UV‐visible) absorption, synchronous fluorescence, and circular dichroism (CD) spectra reflected that the presence of maltol caused conformational change of CAT and made the CAT molecule skeleton loose and increased α‐helix of CAT. Maltol mainly bound with CAT through hydrogen bond, and binding site that is near the heme ring in the enzyme activity center did not interact with its main amino acid residues. This study explores the combination between maltol and CAT, providing references for evaluating health damages caused by maltol.  相似文献   
23.
Nitrogen (N) is one of the most important factors limiting plant productivity, and N fixation by legume species is an important source of N input into ecosystems. Meanwhile, N resorption from senescent plant tissues conserves nutrients taken up in the current season, which may alleviate ecosystem N limitation. N fixation was assessed by the 15N dilution technique in four types of alpine grasslands along the precipitation and soil nutrient gradients. The N resorption efficiency (NRE) was also measured in these alpine grasslands. The aboveground biomass in the alpine meadow was 4–6 times higher than in the alpine meadow steppe, alpine steppe, and alpine desert steppe. However, the proportion of legume species to community biomass in the alpine steppe and the alpine desert steppe was significantly higher than the proportion in the alpine meadow. N fixation by the legume plants in the alpine meadow was 0.236 g N/m2, which was significantly higher than N fixation in other alpine grasslands (0.041 to 0.089 g N/m2). The NRE in the alpine meadows was lower than in the other three alpine grasslands. Both the aboveground biomass and N fixation of the legume plants showed decreasing trends with the decline of precipitation and soil N gradients from east to west, while the NRE of alpine plants showed increasing trends along the gradients, which indicates that alpine plants enhance the NRE to adapt to the increasing droughts and nutrient‐poor environments. The opposite trends of N fixation and NRE along the precipitation and soil nutrient gradients indicate that alpine plants adapt to precipitation and soil nutrient limitation by promoting NRE (conservative nutrient use by alpine plants) rather than biological N fixation (open sources by legume plants) on the north Tibetan Plateau.  相似文献   
24.
Knowledge regarding the relationship between the molecular mechanisms underlying atherosclerosis (AS) and transfer RNA-derived small RNAs (tsRNAs) is limited. This study illustrated the expression profile of tsRNAs, thus exploring its roles in AS pathogenesis. Small RNA sequencing was performed with four atherosclerotic arterial and four healthy subject samples. Using bioinformatics, the protein-protein interaction network and cellular experiments were constructed to predict the enriched signalling pathways and regulatory roles of tsRNAs in AS. Of the total 315 tsRNAs identified to be dysregulated in the AS group, 131 and 184 were up-regulated and down-regulated, respectively. Interestingly, the pathway of the differentiated expression of tsRNAs in cell adhesion molecules (CAMs) was implicated to be closely associated with AS. Particularly, tRF-Gly-GCC might participate in AS pathogenesis via regulating cell adhesion, proliferation, migration and phenotypic transformation in HUVECs and VSMCs. In conclusion, tsRNAs might help understand the molecular mechanisms of AS better. tRF-Gly-GCC may be a promising target for suppressing abnormal vessels functions, suggesting a novel strategy for preventing the progression of atherosclerosis.  相似文献   
25.
βII spectrin, the most common isoform of non-erythrocyte spectrin, is a cytoskeleton protein present in all nucleated cells. Interestingly, βII spectrin is essential for the development of various organs such as nerve, epithelium, inner ear, liver and heart. The functions of βII spectrin include not only establishing and maintaining the cell structure but also regulating a variety of cellular functions, such as cell apoptosis, cell adhesion, cell spreading and cell cycle regulation. Notably, βII spectrin dysfunction is associated with embryonic lethality and the DNA damage response. More recently, the detection of altered βII spectrin expression in tumors indicated that βII spectrin might be involved in the development and progression of cancer. Its mutations and disorders could result in developmental disabilities and various diseases. The versatile roles of βII spectrin in disease have been examined in an increasing number of studies; nonetheless, the exact mechanisms of βII spectrin are still poorly understood. Thus, we summarize the structural features and biological roles of βII spectrin and discuss its molecular mechanisms and functions in development, homeostasis, regeneration and differentiation. This review highlight the potential effects of βII spectrin dysfunction in cancer and other diseases, outstanding questions for the future investigation of therapeutic targets. The investigation of the regulatory mechanism of βII spectrin signal inactivation and recovery may bring hope for future therapy of related diseases.  相似文献   
26.
Emerging lines of evidence have shown that blockade of ubiquitin-proteasome system (UPS) activates autophagy. The molecular players that regulate the relationship between them remain to be elucidated. Bcl-2 associated athanogene 3 (BAG3) is a member of the BAG co-chaperone family that regulates the ATPase activity of heat shock protein 70 (HSP70) chaperone family. Studies on BAG3 have demonstrated that it plays multiple roles in physiological and pathological processes, including antiapoptotic activity, signal transduction, regulatory role in virus infection, cell adhesion and migration. Recent studies have attracted much attention on its role in initiation of autophagy. The current study, for the first time, demonstrates that proteasome inhibitors elicit noncanonical autophagy, which was not suppressed by inhibitors of class III phosphatidylinositol 3-kinase (PtdIns3K) or shRNA against Beclin 1 (BECN1). In addition, we demonstrate that BAG3 is ascribed to activation of autophagy elicited by proteasome inhibitors and MAPK8/9/10 (also known as JNK1/2/3 respectively) activation is also implicated via upregulation of BAG3. Moreover, we found that noncanonical autophagy mediated by BAG3 suppresses responsiveness of HepG2 cells to proteasome inhibitors.  相似文献   
27.
Approximately 10–15% of individuals infected with Helicobacter pylori will develop ulcer disease (gastric or duodenal ulcer), while most people infected with H. pylori will be asymptomatic. The majority of infected individuals remain asymptomatic partly due to the inhibition of synthesis of cholesteryl α-glucosides in H. pylori cell wall by α1,4-GlcNAc-capped mucin O-glycans, which are expressed in the deeper portion of gastric mucosa. However, it has not been determined how cholesteryl α-glucosyltransferase (αCgT), which forms cholesteryl α-glucosides, functions in the pathogenesis of H. pylori infection. Here, we show that the activity of αCgT from H. pylori clinical isolates is highly correlated with the degree of gastric atrophy. We investigated the role of cholesteryl α-glucosides in various aspects of the immune response. Phagocytosis and activation of dendritic cells were observed at similar degrees in the presence of wild-type H. pylori or variants harboring mutant forms of αCgT showing a range of enzymatic activity. However, cholesteryl α-glucosides were recognized by invariant natural killer T (iNKT) cells, eliciting an immune response in vitro and in vivo. Following inoculation of H. pylori harboring highly active αCgT into iNKT cell-deficient (Jα18−/−) or wild-type mice, bacterial recovery significantly increased in Jα18−/− compared to wild-type mice. Moreover, cytokine production characteristic of Th1 and Th2 cells dramatically decreased in Jα18−/− compared to wild-type mice. These findings demonstrate that cholesteryl α-glucosides play critical roles in H. pylori-mediated gastric inflammation and precancerous atrophic gastritis.  相似文献   
28.
The biocontrol properties of Trichoderma species are well documented, but their effectiveness in antagonism of the problematic Sclerotium cepivorum, the causal agent of white rot in Allium species, appears limited with reports of significant control only relating to deliberately-mutated strains of Trichoderma. Our previous studies have indicated the possibility of using selected naturally-occurring strains of the antagonist in the suppression of other diseases; now in vitro and controlled environment in vivo studies have indicated that a degree of control of Onion White Rot is possible, and that the selected antagonist strains can be used in integrated treatments with Iprodione to good effect. The possible value of such treatments is considered in light of other approaches to the suppression of this continuing problem.  相似文献   
29.
In this study, the early stage of interfacial crystallisation behaviour of low molecular weight polyethylene (PE) and isotactic polypropylene (iPP) oligomer on the surface of carbon nanotubes (CNTs) with different diameters, chiralities and topography structures was studied using MD simulations. We started to simulate the effect of CNTs chirality and diameter on PE molecular chain orientation, and then the effect of CNTs topography structure on PE and iPP molecular chain orientation was investigated. Finally, some experiments were carried out to prove the simulated results. Our study shows that for CNTs with a diameter comparable with the radius of gyration (Rg) of a polymer chain, an easy orientation of PE chains along CNTs axis is observed for all the systems of the CNTs with different chiralities due to a geometric confinement effect. For CNTs with a much larger diameter, multiple orientation of PE chains is induced on its surface due to the lattice matching between graphite lattice and PE molecular chains. In this case, the chirality of CNTs dominates the orientation of graphite lattice, which determines the orientation of PE chains arrangement on CNTs surface. More importantly, it was found that the groove structure formed by CNT bundles is very useful for the stabilisation of polymer chain, and thus facilitates the orientation of molecular chain along the long axis of CNTs. As a result, a novel nanohybrid shish–kebab (NHSK) structure with CNTs acting as central shish while polymer lamellae as kebab can be successfully obtained for both PE with zigzag conformation and iPP with helical conformation. This simulation result was well supported by the experimental observation. Our study could provide not only a deep understanding of the origin of the polymer chain orientation on CNTs surface but also the guidance for the preparation of polymer/CNTs nanocomposites with novel NHSK structure.  相似文献   
30.
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