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   9154篇
  免费   691篇
  国内免费   782篇
  10627篇
  2024年   20篇
  2023年   130篇
  2022年   298篇
  2021年   506篇
  2020年   309篇
  2019年   442篇
  2018年   401篇
  2017年   252篇
  2016年   428篇
  2015年   589篇
  2014年   697篇
  2013年   786篇
  2012年   882篇
  2011年   761篇
  2010年   436篇
  2009年   434篇
  2008年   454篇
  2007年   396篇
  2006年   357篇
  2005年   257篇
  2004年   248篇
  2003年   202篇
  2002年   148篇
  2001年   133篇
  2000年   121篇
  1999年   102篇
  1998年   100篇
  1997年   91篇
  1996年   83篇
  1995年   71篇
  1994年   64篇
  1993年   46篇
  1992年   78篇
  1991年   47篇
  1990年   33篇
  1989年   37篇
  1988年   22篇
  1987年   25篇
  1986年   25篇
  1985年   24篇
  1984年   11篇
  1983年   9篇
  1982年   10篇
  1981年   6篇
  1980年   5篇
  1979年   9篇
  1976年   4篇
  1973年   5篇
  1971年   4篇
  1968年   6篇
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
51.
真核细胞对外界压力刺激会做出一系列应答反应,如暂停蛋白质翻译系统,从而使细胞能更好地适应环境压力。通过应激颗粒(stress granules,SG)的形成包裹未被翻译的mRNA是该适应性调节的重要方式。研究表明,环境压力导致eIF2α上游激酶的激活从而磷酸化eIF2α,翻译起始受阻,随后,TIA-1、TTP等蛋白迅速与mRNP结合聚集成SG,并在微管蛋白的帮助下进一步向细胞核聚集,形成成熟的SG。当压力消失,SG依赖微管及其动力蛋白进行解聚,释放包裹的mRNA及蛋白。细胞内成熟的SG在转录后调节中发挥重要作用,并且通过其组成蛋白在肿瘤凋亡、病毒侵染、免疫、炎症反应及由蛋白错误折叠引起的疾病中发挥作用。该文首次综述了压力颗粒研究进展,为充分认识SG的病理生理性调节功能提供参考。  相似文献   
52.
对山西省朔县省虹鳟试验场1987年8月在亲鱼中爆发的一次流行病进行了病原菌分离、培养、毒力试验和详细的生理生化测定,确定点状气单胞菌为其病原菌。并对该菌胞外产物的致病性进行了研究,通过测定其溶血活性、酪蛋白酶活性、对鱼致死性以及对其引起的组织病理学变化的观察,初步确定了胞外产物与该菌侵袭力的相关性。  相似文献   
53.
从酵母中提取谷胱甘肽的初步研究   总被引:28,自引:3,他引:28  
周楠迪  李寅 《生物技术》1997,7(4):30-33,48
考察了不同提取方法对从酵母中提取谷胱甘肽(GSH)的影响,热水抽提由于其提取收率高(90%),耗时短(10min)经济性强而明显优于其它提取方法,对732阳离子交换树脂纯化GSH进行了初步研究,主要研究了树脂颗粒大小对提纯GSH的影响,采用60~80目的树脂,GSH收率为57.6%,虽然比80目以上的树脂低10%但前者操作作所需时间只有后者的1/3。  相似文献   
54.
Amidated neuropeptides play essential roles throughout the nervous and endocrine systems. Mice lacking peptidylglycine α-amidating monooxygenase (PAM), the only enzyme capable of producing amidated peptides, are not viable. In the amidation reaction, the reactant (glycine-extended peptide) is converted into a reaction intermediate (hydroxyglycine-extended peptide) by the copper-dependent peptidylglycine-α-hydroxylating monooxygenase (PHM) domain of PAM. The hydroxyglycine-extended peptide is then converted into amidated product by the peptidyl-α-hydroxyglycine α-amidating lyase (PAL) domain of PAM. PHM and PAL are stitched together in vertebrates, but separated in some invertebrates such as Drosophila and Hydra. In addition to its luminal catalytic domains, PAM includes a cytosolic domain that can enter the nucleus following release from the membrane by γ-secretase. In this work, several glycine- and hydroxyglycine-extended peptides as well as amidated peptides were qualitatively and quantitatively assessed from pituitaries of wild-type mice and mice with a single copy of the Pam gene (PAM(+/-)) via liquid chromatography-mass spectrometry-based methods. We provide the first evidence for the presence of a peptidyl-α-hydroxyglycine in vivo, indicating that the reaction intermediate becomes free and is not handed directly from PHM to PAL in vertebrates. Wild-type mice fed a copper deficient diet and PAM(+/-) mice exhibit similar behavioral deficits. While glycine-extended reaction intermediates accumulated in the PAM(+/-) mice and reflected dietary copper availability, amidated products were far more prevalent under the conditions examined, suggesting that the behavioral deficits observed do not simply reflect a lack of amidated peptides.  相似文献   
55.
Crimean-Congo hemorrhagic fever virus (CCHFV) is a causative agent of serious hemorrhagic diseases in humans with high mortality rates. CCHFV glycoprotein Gc plays critical roles in mediating virus-host membrane fusion and has been studied extensively as an immunogen. However, the molecular mechanisms involved in membrane fusion and Gc-specific antibody-antigen interactions remain unresolved largely because structural information of this glycoprotein is missing. We designed a trimeric protein including most of the ectodomain region of Gc from the prototype CCHFV strain, IbAr10200, which enabled the cryo-electron microscopy structure to be solved at a resolution of 2.8 ?. The structure confirms that CCHFV Gc is a class II fusion protein. Unexpectedly, structural comparisons with other solved Gc trimers in the postfusion conformation revealed that CCHFV Gc adopted hybrid architectural features of the fusion loops from hantaviruses and domain III from phenuiviruses, suggesting a complex evolutionary pathway among these bunyaviruses. Antigenic sites on CCHFV Gc that protective neutralizing antibodies target were mapped onto the CCHFV Gc structure, providing valuable information that improved our understanding of potential neutralization mechanisms of various antibodies.  相似文献   
56.
<正>Streptomycetes are Gram-positive bacteria with high GC DNA content. They produce the most abundant secondary metabolites including over two-thirds of the clinically used antibiotics of natural origin (Barka et al., 2016), for example,the important broad-spectrum antimicrobials oxytetracycline(OTC) and chlortetracycline, which are the tetracycline antibiotics, produced by Streptomyces rimosus and Strepto-  相似文献   
57.
CCL5 (previously called RANTES) is in the CC‐chemokine family and plays a crucial role in the migration and metastasis of human cancer cells. On the other hand, the effect of CCL5 is mediated via CCR receptor. RT‐PCR and flow cytometry studies demonstrated CCR5 but not CCR1 and CCR3 mRNA in oral cancer cell lines, especially higher in those with high invasiveness (SCC4) as compared with lower levels in HSC3 cells and SCC9 cells. Stimulation of oral cancer cells with CCL5 directly increased the migration and metalloproteinase‐9 (MMP‐9) production. MMP‐9 small interfering RNA inhibited the CCL5‐induced MMP‐9 expression and thereby significantly inhibited the CCL5‐induced cell migration. Activations of phospholipase C (PLC), protein kinase Cδ (PKCδ), and NF‐κB pathways after CCL5 treatment was demonstrated, and CCL5‐induced expression of MMP‐9 and migration activity was inhibited by the specific inhibitor of PLC, PKCδ, and NF‐κB cascades. In addition, migration‐prone sublines demonstrate that cells with increasing migration ability had more expression of MMP‐9, CCL5, and CCR5. Taken together, these results indicate that CCL5/CCR5 axis enhanced migration of oral cancer cells through the increase of MMP‐9 production. J. Cell. Physiol. 220: 418–426, 2009. © 2009 Wiley‐Liss, Inc.  相似文献   
58.
从中国发病鸡中分离的鸡减蛋综合征病毒(EggDropSyndromVirus,EDSV)弱毒株(AA-2),其基因组全长约为33kb。用限制性内切酶HindⅢ水解EDSV全基因组,构建了以pBluescriptⅡ(KS+)为载体的右末端片段的克隆(约4.2kb),对其进行了序列测定和结构分析。该片段全长4183个碱基对(bp),位于基因组右末端87.3m.u.-100m.u.。结果显示,该片段与哺乳动物腺病毒右末端E4区结构不同,与禽Ⅰ型腺病毒代表株CELO右末端片段亦无同源性。本文为深入了解EDSV基因组结构特点,EDSV与其他腺病毒基因结构与功能的进化关系和EDSV载体的构建奠定了分子生物学基础  相似文献   
59.
The process of preadipocytes differentiation plays a vital role in adipose tissue expansion and many factors are involved in this event. Cathepsin B (CTSB), secreted from lysosome, has been reported in regulating a variety of physiological processes. In this study, we demonstrated CTSB promotes lipid accumulation and adipogenic genes expression in porcine primary preadipocytes by degrading fibronectin (Fn), a key component of extracellular matrix. Lithium chloride (LiCl) is an activator of Wnt/β-catenin signaling through stabilizing β-catenin. We found that CTSB can relieve the anti-adipogenic effects of LiCl, indicating that CTSB could impact Wnt/β-catenin signaling pathway. Interestingly, Fn is an important target gene of Wnt/β-catenin. So we considered that CTSB promote preadipocytes differentiation by suppressing these two pathways.  相似文献   
60.
降解三硝基甲苯的酵母和类酵母菌的研究   总被引:9,自引:0,他引:9  
从受三硝基甲苯(TNT)严重污染的土壤和废水中分离筛选到17株可降解TNT的酵母菌和白地霉。其中6株为克鲁斯假丝酵母(Candidakrusei),4株为橡树假丝酵母(C.quercitrusa),一株为无名假丝酵母(C.famata),一株为伯杰汉逊酵母(Hansenulabeijerinckii),一株为亚膜汉逊酵母(H.subpelliculosa),4株为白地霉(Geotrichumcandidum)。对其中6株菌进行了降解TNT的条件实验,发现降解TNT的适宜pH为7,温度为37~40℃。在含75~80mg/LTNT的培养基中,40h内能降解TNT56~74mg/L,去除率达71%~93%。在培养基中加入0.01%~0.05%的葡萄糖作碳源,或加入0.01%~0.1%的酵母膏对6株菌降解TNT的能力略有促进作用。加入铵盐作为氮源则明显抑制这些菌对TNT的降解。  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