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   8271篇
  免费   654篇
  国内免费   599篇
  9524篇
  2024年   16篇
  2023年   104篇
  2022年   267篇
  2021年   436篇
  2020年   308篇
  2019年   348篇
  2018年   370篇
  2017年   251篇
  2016年   357篇
  2015年   503篇
  2014年   571篇
  2013年   599篇
  2012年   761篇
  2011年   633篇
  2010年   384篇
  2009年   369篇
  2008年   408篇
  2007年   378篇
  2006年   347篇
  2005年   276篇
  2004年   237篇
  2003年   203篇
  2002年   175篇
  2001年   142篇
  2000年   114篇
  1999年   134篇
  1998年   80篇
  1997年   90篇
  1996年   81篇
  1995年   74篇
  1994年   85篇
  1993年   60篇
  1992年   73篇
  1991年   69篇
  1990年   60篇
  1989年   33篇
  1988年   36篇
  1987年   25篇
  1986年   19篇
  1985年   23篇
  1984年   9篇
  1983年   11篇
  1982年   1篇
  1981年   1篇
  1980年   2篇
  1978年   1篇
排序方式: 共有9524条查询结果,搜索用时 15 毫秒
101.
102.
昆虫体内储存蛋白的研究进展   总被引:1,自引:0,他引:1  
储存蛋白是昆虫体内普遍存在的一种特异性血淋巴蛋白 ,通常在幼虫的脂肪体内合成 ,释放进入血淋巴中。化蛹时 ,又被脂肪体选择性吸收 ,作为氨基酸的贮存库对成虫变态发育和雌性卵发育起着重要的作用。该文介绍了昆虫体内储存蛋白的特性、功能、及调节机制。  相似文献   
103.
Myelin-derived proteins, such as tenascin-R (TN-R), myelin associate glycoprotein (MAG), oligodendrocyte-myelin glycoprotein (OMgp), and Nogo-A, inhibit the central nervous system regeneration. In this study, the DNA vaccine encoding for oligodendrocyte and myelin-related antigens was employed to attenuate the axonal growth inhibitory properties of myelin in the setting of spinal cord injury. Using a rat spinal cord dorsal hemisection model, the vaccine directed against the inhibitory epitopes of Nogo-A, MAG, OMgp, and TN-R was administered intramuscularly once a week following spinal cord injury, supplemented with local application of specific anti-sera against the four antigens. Anterograde labeling of dorsal column fibers showed active axonal regeneration through the lesion site at the eighth week following the treatment in experimental group but not in control groups. Light microscopic and ultrastructural analysis revealed that vaccination with these myelin-related antigens did not lead to demyelinating disease. OMgp and TN-R levels were down-regulated at the lesion site together with a parallel increase in growth-associated protein 43 levels in the treatment groups. This study reveals the effective approach of a DNA vaccine strategy by attaining the special antibody to direct neutralization of the myelin inhibitors during spinal cord injury.  相似文献   
104.
Glucose oxidation modulates anoikis and tumor metastasis   总被引:1,自引:0,他引:1  
Cancer cells exhibit altered glucose metabolism characterized by a preference for aerobic glycolysis or the Warburg effect, and the cells resist matrix detachment-induced apoptosis, which is called anoikis, a barrier to metastasis. It remains largely unclear whether tumor metabolism influences anoikis and metastasis. Here we show that when detached from the matrix, untransformed mammary epithelial cells undergo metabolic reprogramming by markedly upregulating pyruvate dehydrogenase (PDH) kinase 4 (PDK4) through estrogen-related receptor gamma (ERRγ), thereby inhibiting PDH and attenuating the flux of glycolytic carbon into mitochondrial oxidation. To decipher the significance of this metabolic response, we found that depletion of PDK4 or activation of PDH increased mitochondrial respiration and oxidative stress in suspended cells, resulting in heightened anoikis. Conversely, overexpression of PDKs prolonged survival of cells in suspension. Therefore, decreased glucose oxidation following cell detachment confers anoikis resistance. Unlike untransformed cells, most cancer cells demonstrate reduced glucose oxidation even under attached conditions, and thus they inherently possess a survival advantage when suspended. Normalization of glucose metabolism by stimulating PDH in cancer cells restores their susceptibility to anoikis and impairs their metastatic potential. These results suggest that the Warburg effect, more specifically, diminished glucose oxidation, promotes anoikis resistance and metastasis and that PDKs are potential targets for antimetastasis therapy.  相似文献   
105.
The molecular mechanisms responsible for the loss of dopaminergic neurons in Parkinson’s disease (PD) remain obscure. Loss of function of E3 ubiquitin ligases is associated with mitochondria dysfunction, dysfunction of protein degradation, and α-synuclein aggregation, which are major contributors to neurodegeneration in PD. Recent research has thus focused on E3 ubiquitin ligase glycoprotein 78 (GP78); however, the role of GP78 in PD pathogenesis remains unclear. Notably, cyclin-dependent kinase 5 (CDK5) controls multiple cellular events in postmitotic neurons, and CDK5 activity has been implicated in the pathogenesis of PD. Thus, we addressed the relationship between CDK5 and GP78 in MPTP-based PD models. We found that GP78 expression is decreased in MPTP-based cellular and animal PD models, and CDK5 directly phosphorylated GP78 at Ser516, which promoted the ubiquitination and degradation of GP78. Importantly, overexpression of GP78 or interference of GP78 Ser516 phosphorylation protected neurons against MPP+-induced cell death. Thus, our research reveals that the CDK5-GP78 pathway is involved in the pathogenesis of PD and could be a novel candidate drug target for the treatment of PD.  相似文献   
106.
Based on the change in electrochemical behavior of enzymatic activity induced by pesticide, a novel electrochemical method has been devised for investigation of pesticide sensitivity using acetylcholinesterase (AChE) biosensor. Because of the excellent biocompatibility and good stability of chitosan matrix, it prevented leakage of the AChE from electrode. Multiwall carbon nanotube (MWNT) promoted electron transfer reaction at a lower potential and catalyzed the electro-oxidation of thiocholine, thus amplifying the sensitivity and amperometric response of the biosensor. Four pesticides of carbaryl, malathion, dimethoate and monocrotophos were selected to discuss their inhibition efficiencies to AChE. The inhibition curves were similar to Michealis-Menten and the Michealis-Menten constants (Km) were calculated to be 0.96 microM, 1.78 microM, 1.97 microM and 4.28 microM, respectively. Ninety-five percent reactivation of the inhibited AChE could be regenerated using pralidoxime iodide within 8 min. The proposed electrochemical pesticide sensitivity test exhibited high sensitivity, low cost and simplified procedures, which is a promising new tool for comparison of pesticide sensitivity and for selection of the most efficient enzyme inhibitors.  相似文献   
107.
Liu C  Cai L  Han X  Ying T 《Gene》2011,486(1-2):56-64
To obtain an overall view on gene expression during the early stage (24 h) of tomato fruit in response to postharvest UV-C irradiation (4 kJ/m(2)), we performed a microarray analysis by using Affymetrix Tomato Genechip. The results showed that 274 and 403 genes were up- or down-regulated, respectively, more than two folds in postharvest tomato fruit irradiated with UV-C as compared with that in control fruit. The up-regulated genes mainly involve in signal transduction, defense response and metabolism. Conversely, genes related to cell wall disassembly, photosynthesis and lipid metabolism were generally down-regulated. These results opened ways to probe into the molecular mechanisms of the effects of postharvest UV-C irradiation on increased disease resistance, delayed softening, better quality maintenance and prolonged postharvest life in tomato fruit.  相似文献   
108.
蔡联炳 《植物研究》1996,16(3):273-280
叶片表皮、叶片横切面、花粉和淀粉粒的微观特征,对青藏高原的特有类群三蕊草属Sinochasea Keng的系统位置进行了探讨。结果表明,三蕊草S.trigyna Keng在上述微观性状上与毛蕊草Duthiea brachypodia(P.Candargy) Keng et Keng f.差距最小,与冠毛草Stephanachne pappophorea(Hack.)Keng差距次之,与宝兴野青茅Deyeuxia moupinensis(Franch.) Pilger和拂子茅Calamagrostis epigeios(L.) Roth差距最大;三蕊草属的系统位置应处于毛蕊草所隶的燕麦族Aveneae中;在系统演化上,燕麦族是最原始的类群,它可能直接或间接地派生了针茅族Stipeae和剪股颖族Agrostideae。  相似文献   
109.
长春花黄化植原体(PY)株系的检测与鉴定   总被引:7,自引:0,他引:7  
植原体 (Phytoplasma) (原称类菌原体Mycoplasma likeOrganism ,简称MLO)是一类无细胞壁、存在于植物筛管细胞内的原核生物。植原体自 1 967年被日本学者土居养二首次发现后 ,迄今为止 ,世界上报道的植物植原体病害多达 30 0余种 ,早期对植原体的鉴定主要是通过生物学特性 ,如症状特征、与昆虫介体的相互关系等进行的。这些方法费时费力 ,结果往往也不是很可靠。 80年代 ,随着血清学、分子探针以及PCR技术的发展应用 ,为植原体的检测提供了一种相对简单、灵敏、可靠的方法。通过对 1 6SrRNA基…  相似文献   
110.
Accurate assessment of human epidermal growth factor receptor (HER) 2 is essential for efficient selection of patients who may benefit from therapies targeting this surface receptor (e.g., trastuzumab). Intratumoral heterogeneity of HER2 expression may potentially contribute to inaccurate assessment of HER2 status. To clarify intratumoral heterogeneity of HER2 expression and its potential clinical impact on assessment of HER2 status, we analyzed 148 endoscopic biopsy specimens and 117 excisional tumor specimens collected from 148 patients with primary gastric cancer. Specifically, we assessed HER2 protein overexpression and gene amplification using, respectively, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). There were 28 IHC-positive cases and 25 FISH-positive cases among these 148 patients. Heterogeneous HER2 protein expression was demonstrated in 23 of 29 (79.3%) IHC-positive cases, while gene expression heterogeneity was found in 11 of 25 (44.0%) FISH-positive cases. Intratumoral heterogeneity was the main reason of discordant results between IHC and FISH or between endoscopic biopsy and excisional tumor specimens. The clinical significance and impact of intratumoral HER2 expression heterogeneity on treatment outcome in gastric cancer require further studies.  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