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   1656篇
  免费   123篇
  国内免费   59篇
  2023年   7篇
  2022年   48篇
  2021年   68篇
  2020年   37篇
  2019年   57篇
  2018年   53篇
  2017年   41篇
  2016年   72篇
  2015年   106篇
  2014年   115篇
  2013年   117篇
  2012年   151篇
  2011年   121篇
  2010年   83篇
  2009年   67篇
  2008年   70篇
  2007年   83篇
  2006年   64篇
  2005年   73篇
  2004年   57篇
  2003年   58篇
  2002年   48篇
  2001年   39篇
  2000年   20篇
  1999年   32篇
  1998年   16篇
  1997年   8篇
  1996年   12篇
  1995年   13篇
  1994年   15篇
  1993年   9篇
  1992年   10篇
  1991年   14篇
  1990年   6篇
  1989年   9篇
  1988年   4篇
  1987年   4篇
  1986年   9篇
  1985年   2篇
  1984年   4篇
  1983年   4篇
  1980年   1篇
  1976年   3篇
  1975年   2篇
  1974年   1篇
  1973年   1篇
  1972年   2篇
  1970年   2篇
排序方式: 共有1838条查询结果,搜索用时 203 毫秒
51.
Prohibitins (PHBs) are ubiquitously expressed conserved proteins in eukaryotes that are associated with apoptosis, cancer formation, aging, stress responses, cell proliferation, and immune regulation. However, the function of PHBs in crustacean immunity remains largely unknown. In the present study, we identified a PHB in Procambarus clarkii red swamp crayfish, which was designated PcPHB1. PcPHB1 was widely distributed in several tissues, and its expression was significantly upregulated by white spot syndrome virus (WSSV) challenge at the mRNA level and the protein level. These observations prompted us to investigate the role of PcPHB1 in the crayfish antiviral response. Recombinant PcPHB1 (rPcPHB1) significantly reduced the amount of WSSV in crayfish and the mortality of WSSV-infected crayfish. The quantity of WSSV in PcPHB1 knockdown crayfish was increased compared with that in the controls. The effects of RNA silencing were rescued by rPcPHB1 reinjection. We further confirmed the interaction of PcPHB1 with the WSSV envelope proteins VP28, VP26, and VP24 using pulldown and far-Western overlay assays. Finally, we observed that the colloidal gold-labeled PcPHB1 was located on the outer surface of the WSSV, which suggests that PcPHB1 specifically binds to the envelope proteins of WSSV. VP28, VP26, and VP24 are structural envelope proteins and are essential for attachment and entry into crayfish cells. Therefore, PcPHB1 exerts its anti-WSSV effect by binding to VP28, VP26, and VP24, preventing viral infection. This study is the first report on the antiviral function of PHB in the innate immune system of crustaceans.  相似文献   
52.
53.
The heavy metal Cadmium (Cd), added to the water bodies through weathering of rocks and human activities, constitutes one of the major environmental pollutants toxic to plants. This study examines the proteome changes in roots of actively growing Kandelia candel (L.) Druce when challenged with Cd. This mangrove-like species proliferates in estuaries and bays and is a potential choice for phytoremediation of Cd. A total of 53 proteins were up- or down-regulated following a short-term Cd treatment. The identities of the differentially expressed proteins were determined by MALDI-TOF/TOF. Approximately half of the up-regulated proteins are involved in oxidative response, including antioxidant enzymes, enzymes required for glutathione biosynthesis, enzymes in TCA and PPP cycles for generating ATP, NADH and NADPH. These results support the prediction that a prompt antioxidative response is necessary for the reduction of the oxidative stress caused by Cd and set the stage for further investigating of Cd up-regulated proteins in Kandelia candel.  相似文献   
54.
T cell receptors (TCRs) are immune proteins that specifically bind to antigenic molecules, which are often foreign peptides presented by major histocompatibility complex proteins (pMHCs), playing a key role in the cellular immune response. To advance our understanding and modeling of this dynamic immunological event, we assembled a protein–protein docking benchmark consisting of 20 structures of crystallized TCR/pMHC complexes for which unbound structures exist for both TCR and pMHC. We used our benchmark to compare predictive performance using several flexible and rigid backbone TCR/pMHC docking protocols. Our flexible TCR docking algorithm, TCRFlexDock, improved predictive success over the fixed backbone protocol, leading to near‐native predictions for 80% of the TCR/pMHC cases among the top 10 models, and 100% of the cases in the top 30 models. We then applied TCRFlexDock to predict the two distinct docking modes recently described for a single TCR bound to two different antigens, and tested several protein modeling scoring functions for prediction of TCR/pMHC binding affinities. This algorithm and benchmark should enable future efforts to predict, and design of uncharacterized TCR/pMHC complexes.  相似文献   
55.
通过野外调查、标本采集、分类学研究及资料考证,对六盘水酸模属植物的资源进行了调查.结果表明,六盘水有酸模属植物7种,其中钝叶酸模(Rumex obtusifoliusL.)为贵州省的分布新纪录,并对酸模属植物药用价值、食用价值及生态价值等进行了分析.  相似文献   
56.
57.
【目的】通过基因组挖掘的方法,研究红树林来源白骨壤链霉菌Streptomyces avicenniae 9-9中多环稠合大环内酰胺(PTMs)类化合物的结构多样性。【方法】通过生物信息学分析白骨壤链霉菌基因组序列,寻找PTMs类化合物的生物合成相关基因;利用UPLC-MS/MS技术对该菌的次级代谢产物进行分析。【结果】在白骨壤链霉菌基因组中发现PTMs生物合成基因簇(aviA-D);从菌液提取物中鉴定出5个PTMs类化合物,其中包括ikarugamycin(化合物1)和capsimycin B(化合物2);基于PTMs类化合物5-6-5环类型的MS/MS碎裂规律,对化合物3–5的结构进行了推测。【结论】红树林来源白骨壤链霉菌S.avicenniae 9-9具有产生5-6-5环类型的PTMs类化合物的能力。  相似文献   
58.
The derivatives of 1,4‐dimethoxybenzene are thus far the best performing redox shuttle additives for overcharge protection of Li‐ion batteries. The most durable molecules of this kind typically possess two in‐plane methoxy groups that are equivalent by inversion symmetry. However, such geometry leads to a vanishing average dipole moment that causes poor solubility of these molecules in carbonate‐based electrolytes. In this study, a novel redox shuttle additive, 1,2,3,4‐tetrahydro‐6,7‐dimethoxy‐1,1,4,4‐tetramethyl‐naphthalene (TDTN), is introduced. It has been demonstrated that reversible oxidation at 4.05 V versus Li+/Li, high polarity, high solubility (around 0.4 m ), and excellent electrochemical stability (150 overcharge cycles at C/2 rate with 100% overcharge) can all be achieved simultaneously by the imposition of axial symmetry in the corresponding radical cation that is generated by electrochemical oxidation of TDTN in the battery. The intricate interplay between the symmetry and the chemical stability of the radical cation is scrutinized using magnetic resonance spectroscopy and electron structure modeling.  相似文献   
59.
Enzyme catalysis has been studied for over a century. How it actually occurs has not been visualized until recently. By combining in crystallo reaction and X-ray diffraction analysis of reaction intermediates, we have obtained unprecedented atomic details of the DNA synthesis process. Contrary to the established theory that enzyme-substrate complexes and transition states have identical atomic composition and catalysis occurs by the two-metal-ion mechanism, we have discovered that an additional divalent cation has to be captured en route to product formation. Unlike the canonical two metal ions, which are coordinated by DNA polymerases, this third metal ion is free of enzyme coordination. Its location between the α- and β-phosphates of dNTP suggests that the third metal ion may drive the phosphoryltransfer from the leaving group opposite to the 3′-OH nucleophile. Experimental data indicate that binding of the third metal ion may be the rate-limiting step in DNA synthesis and the free energy associated with the metal-ion binding can overcome the activation barrier to the DNA synthesis reaction.  相似文献   
60.

Background

There are few data on the prevalence of obesity and its influence on achieving blood glucose, blood pressure, and blood lipid (3B) goals in Chinese type 2 diabetes outpatients.

Methods

Patient demographic data, anthropometric measurements, medications, and blood glucose and lipid profiles of 24,512 type 2 diabetes patients from a large, geographically diverse study (CCMR-3B) were analyzed. Using cut-points for body mass index (BMI) and waist circumference (WC) recommended by the Working Group on Obesity in China, overweight and obesity were defined as BMIs of 24–27.9kg/m2 and ≥28.0kg/m2. Central obesity was defined as a waist circumference ≥80cm in women and ≥85cm in men. The 3B therapeutic goals were HbA1c<7.0%, BP<140/90mmHg and LDL-C<2.6mmol/L.

Results

Overall, 43.0% of type 2 diabetes patients were overweight and 16.7% were obese; 13.3% of overweight and and10.1% of obese patients achieved all the 3B target goals. Overweight or obese patients were less likely to achieve 3B goals than those with normal BMIs. More than a half the overweight or obese patients (69.6%) were centrally obese. Patients with abdominal obesity were less likely to achieve cardiometabolic targets than those without abdominal obesity. In multivariate logistic regression analysis, female, higher BMI and waist circumference, smoking, drinking, sedentary lifestyle, and longer diabetes duration were significantly correlated with failure to achieve 3B control goals.

Conclusions

Obesity is highly prevalent and associated with poor 3B control in Chinese type 2 diabetes patients. In clinical practice, more attention and resources should focus on weight loss for such patients.  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