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1.
Interleukin-33 is a newly described member of the interleukin-1 family. Recent research suggests that IL-33 is increased in lungs and plays a critical role in chronic airway inflammation in cigarette smoke-induced chronic obstructive pulmonary disease (COPD) mice. To determine the role of IL-33 in systemic inflammation, we induced COPD mice models by passive cigarette smoking and identified the IL-33 expression in bronchial endothelial cells and peripheral blood mononuclear cells (PBMCs) of them. After isolation, PBMCs were cultured and stimulated in vitro. We measured expressions of interleukin-6 and interleukin-8 in PBMCs in different groups. The expression of IL-33 in bronchial endothelial cells and PBMCs of COPD mice were highly expressed. Stimulated by cigarette smoke extract (CSE), the expression of IL-6 and IL-8 were induced and enhanced by IL-33. PBMCs of COPD mice produced more IL-6 and IL-8 stimulated by CSE and IL-33. Expression of IL-6 and IL-8 were decreased when stimulated by IL-33 together with soluble ST2. The mRNA production of ST2 in IL-33 stimulated PBMCs was increased. Being pretreated with several kinds of MAPK inhibitors, the secretions of IL-6 and IL-8 in PBMCs did not decrease except for the p38 MAPK inhibitor. We found that IL-33 could induce and enhance the expression of IL-6 and IL-8 in PBMCs of COPD mice via p38 MAPK pathway, and it is a promoter of the IL-6 and IL-8 production in systemic inflammation in COPD mice.  相似文献   
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Summary 13C-based three-dimensional 1H–1H correlation experiments have been used to determine essentially complete 13C and 1H resonance assignments for the amino acid side chains of uniformly 13C/15N labelled L. casei dihydrofolate reductase in a complex with the drug methotrexate. Excellent agreement is observed between these assignments and an earlier set of partial assignments made on the basis of correlating nuclear Overhauser effect and crystal structure data, indicating that the tertiary structure of the enzyme is similar in solution and in the crystal state.To whom correspondence should be addressed.  相似文献   
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目的探讨布拉氏酵母菌散对轮状病毒肠炎患儿血清白介素16(IL-6)和肿瘤坏死因子-α(TNF-α)水平的影响及疗效观察。方法选取轮状病毒肠炎患儿84例,随机分为两组(观察组42例和对照组42例)。两组患儿均予以调整饮食、静脉及口服补液、抗病毒及纠正水电解质及酸碱平衡紊乱等常规治疗。观察组患儿加用布拉氏酵母菌散剂治疗,其中〈12个月,0.125g/次,1次/d;≥12个月,0.25g/次,2Oc/a。对照组患儿除不予以布拉氏酵母菌散剂治疗,余治疗药物基本同观察组。治疗3d后,观察两组患儿治疗前后血清细胞因子IL-6和TNF-α水平,并探讨其疗效及不良反应情况。结果治疗3d后,两组患儿血清IL-6和TNF-α水平均比治疗前明显下降(P〈0.05或P〈0.01),且观察组较对照组下降更明显(P〈0.05);同时观察组患儿的临床总有效率(95.24%)明显好于对照组(78.57%)(X2=5.13,P〈0.05),两组患儿治疗期间无明显的药物不良反应发生。结论布拉氏酵母菌散治疗轮状病毒肠炎患儿疗效及安全性均较好,能降低血清细胞因子IL-6和TNF-α表达水平,抑制炎症及免疫反应过程。  相似文献   
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Aminopeptidase N (APN) has been proved to be deeply associated with cancer angiogenesis, metastasis and invasion. Therefore, APN gains increasing attention as a promising anti-tumor target. In the current study, we report the design, synthesis, biological evaluation and structure-activity relationship of one new series of leucine ureido derivatives containing the 1,2,3-triazole moiety. Among them, compound 31f was identified as the best APN inhibitor with IC50 value being two orders of magnitude lower than that of the positive control bestatin. Compound 31f possessed selective cytotoxicity to several tumor cell lines over the normal cell line human umbilical vein endothelial cells (HUVECs). Notably, when combined with 5-fluorouracil (5-Fu), 31f exhibited synergistic anti-proliferation effect against several tumor cell lines. At the same concentration, 31f exhibited much better anti-angiogenesis activities than bestatin in the HUVECs capillary tube formation assay and the rat thoracic aorta rings test. In the in vitro anti-invasion assay, 31f also exhibited superior potency over bestatin. Moreover, considerable in vivo antitumor potencies of 31f alone or in combination with 5-Fu were observed without significant toxic signs in a mouse heptoma H22 tumor transplant model.  相似文献   
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Alaskan seals are found in remote and sometimes inaccessible locations, making it difficult to collect time‐series information. This study explores a novel method to examine temporal changes in diet and physiological status of ringed (Pusa hispida), spotted (Phoca largha), and harbor (Phoca vitulina) seals using cortisol concentrations and δ15N and δ13C stable isotopes (SIs) measured in serial sections of whiskers. As whiskers grow, whisker tissue is deposited sequentially making these measurements temporally aligned. Whisker cortisol presented in a distinct pattern with elevated concentrations at the root section followed by a curvilinear decline moving toward the tip of most whiskers. Comparing SIs at the root to the rest of the whiskers, δ13C values were slightly lower in ringed and harbor seal whiskers and δ15N values were slightly higher in harbor seal whiskers. The data were modeled controlling for the observed trends in cortisol concentrations and further associations between cortisol concentrations and SIs were detected in spotted and harbor seal whiskers. Additional research examining the source and stability of whisker cortisol is warranted. However, the methods presented here demonstrate that whiskers could prove valuable to gather long‐term and naturally aligned dietary and physiological information.  相似文献   
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目的探讨Kruppel样因子4(Kruppel-like factor 4,KLF4)在内毒素血症小鼠中的表达模式及意义。方法运用实时荧光PCR技术和Western blot技术,分别从mRNA水平和蛋白水平探讨内毒素血症小鼠肝脏和肺脏中KLF4的表达;运用生物信息学技术,对启动子区含有KLF4的结合位点的炎症介质基因进行了预测;运用RT-PCR技术,从mRNA水平探讨内毒素血症小鼠肝脏和肺脏中IL1β的表达模式。结果内毒素血症小鼠肝脏和肺脏中KLF4 mRNA的表达下凋,KLF4蛋白的表达先下凋后升高;IL-18、IL-15、IL-12、IL-18、IL-10等炎症介质基因的启动子区均含有KLF4的结合元件,这些炎症基因的表达可能直接受到KLF4的调控;内毒素血症小鼠肝脏和肺脏中IL-IB的表达模式与KLF4的表达模式呈相反趋势。结论内毒素血症小鼠肝脏和肺脏中KLF4表达下调,KLF4在炎症介质基因表达调控中可能具有重要作用。  相似文献   
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Computer-aided antibody engineering has been successful in the design of new biologics for disease diagnosis and therapeutic interventions. Interleukin-6 (IL-6), a well-recognized drug target for various autoimmune and inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, and psoriasis, was investigated in silico to design potential lead antibodies. Here, crystal structure of IL-6 along with monoclonal antibody olokizumab was explored to predict antigen–antibody (Ag???Ab)-interacting residues using DiscoTope, Paratome, and PyMOL. Tyr56, Tyr103 in heavy chain and Gly30, Ile31 in light chain of olokizumab were mutated with residues Ser, Thr, Tyr, Trp, and Phe. A set of 899 mutant macromolecules were designed, and binding affinity of these macromolecules to IL-6 was evaluated through Ag???Ab docking (ZDOCK, ClusPro, and Rosetta server), binding free-energy calculations using Molecular Mechanics/Poisson Boltzman Surface Area (MM/PBSA) method, and interaction energy estimation. In comparison to olokizumab, eight newly designed theoretical antibodies demonstrated better result in all assessments. Therefore, these newly designed macromolecules were proposed as potential lead antibodies to serve as a therapeutics option for IL-6-mediated diseases.  相似文献   
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