全文获取类型
收费全文 | 1658篇 |
免费 | 162篇 |
国内免费 | 210篇 |
专业分类
2030篇 |
出版年
2024年 | 8篇 |
2023年 | 29篇 |
2022年 | 46篇 |
2021年 | 54篇 |
2020年 | 66篇 |
2019年 | 65篇 |
2018年 | 59篇 |
2017年 | 62篇 |
2016年 | 58篇 |
2015年 | 62篇 |
2014年 | 103篇 |
2013年 | 161篇 |
2012年 | 108篇 |
2011年 | 96篇 |
2010年 | 53篇 |
2009年 | 82篇 |
2008年 | 70篇 |
2007年 | 69篇 |
2006年 | 97篇 |
2005年 | 91篇 |
2004年 | 69篇 |
2003年 | 46篇 |
2002年 | 33篇 |
2001年 | 33篇 |
2000年 | 41篇 |
1999年 | 34篇 |
1998年 | 26篇 |
1997年 | 23篇 |
1996年 | 24篇 |
1995年 | 29篇 |
1994年 | 32篇 |
1993年 | 15篇 |
1992年 | 26篇 |
1991年 | 19篇 |
1990年 | 15篇 |
1989年 | 19篇 |
1988年 | 7篇 |
1987年 | 8篇 |
1986年 | 12篇 |
1985年 | 15篇 |
1984年 | 11篇 |
1983年 | 8篇 |
1982年 | 10篇 |
1981年 | 8篇 |
1980年 | 9篇 |
1979年 | 4篇 |
1978年 | 6篇 |
1977年 | 4篇 |
1974年 | 2篇 |
1972年 | 1篇 |
排序方式: 共有2030条查询结果,搜索用时 36 毫秒
31.
32.
Mycoplasmas contain glycoglycerolipids in their plasma membrane as key structural components involved in bilayer properties and stability. A membrane-associated glycosyltransferase (GT), GT MG517, has been identified in Mycoplasma genitalium, which sequentially produces monoglycosyl- and diglycosyldiacylglycerols. When recombinantly expressed in Escherichia coli, the enzyme was functional in vivo and yielded membrane glycolipids from which Glcβ1,6GlcβDAG was identified as the main product. A chaperone co-expression system and extraction with CHAPS detergent afforded soluble protein that was purified by affinity chromatography. GT MG517 transfers glucosyl and galactosyl residues from UDP-Glc and UDP-Gal to dioleoylglycerol (DOG) acceptor to form the corresponding β-glycosyl-DOG, which then acts as acceptor to give β-diglycosyl-DOG products. The enzyme (GT2 family) follows Michaelis-Menten kinetics. k(cat) is about 5-fold higher for UDP-Gal with either DOG or monoglucosyldioleoylglycerol acceptors, but it shows better binding for UDP-Glc than UDP-Gal, as reflected by the lower K(m), which results in similar k(cat)/K(m) values for both donors. Although sequentially adding glycosyl residues with β-1,6 connectivity, the first glycosyltransferase activity (to DOG) is about 1 order of magnitude higher than the second (to monoglucosyldioleoylglycerol). Because the ratio between the non-bilayer-forming monoglycosyldiacylglycerols and the bilayer-prone diglycosyldiacylglycerols contributes to regulate the properties of the plasma membrane, both synthase activities are probably regulated. Dioleoylphosphatidylglycerol (anionic phospholipid) activates the enzyme, k(cat) linearly increasing with dioleoylphosphatidylglycerol concentration. GT MG517 is shown to be encoded by an essential gene, and the addition of GT inhibitors results in cell growth inhibition. It is proposed that glycolipid synthases are potential targets for drug discovery against infections by mycoplasmas. 相似文献
33.
大狼耙草是危害生物多样性的一种恶性杂草。使用使它隆、二甲四氯、草甘膦3种除草剂对大狼耙草进行不同浓度、不同防治时期防除效果研究,结果表明:使它隆对大狼耙草平均致死率为92%,二甲四氯为85%,草甘膦为82%,但三者差异不显著;高、中、低3种浓度(使它隆分别为0.47、0.40、0.33g·L-1,二甲四氯分别为2.80、2.33、1.87g·L-1,草甘膦分别为5.18、3.89、2.59g·L-1)对大狼耙草致死率差异极显著,高浓度溶液防除效果较好;大狼耙草植株在幼苗期(植株高20cm)、生长盛期(植株高40cm)、花期(植株高60cm)3个防治时期致死率差异极显著,幼苗期防除效果理想。研究表明,在大狼耙草幼苗期使用0.47g·L-1浓度的使它隆防除效果最好。 相似文献
34.
临床上,感染性疾病由于诊断不明或诊断时间较长导致严重后果的情况并不罕见。近年来,由于新型病原体感染报道层出不穷,现有病原体出现耐药也十分普遍,导致感染性疾病的诊断和治疗仍是临床上亟待解决的难题。核酸适配体是通过体外反复筛选或指数富集配体系统进化(systematic evolution of ligands by exponential enrichment,SELEX)技术筛选出来的一类具有特异性识别能力的寡核苷酸序列,具有靶向结合目标分子的能力,可用于病原体检测和新型治疗性药物的开发。适配体已在感染性疾病诊治中显现良好的应用前景,进一步推进相关研究有望为感染性疾病的诊治提供新的途径。 相似文献
35.
《Process Biochemistry》2014,49(5):882-889
The VP4 protein of infectious bursal disease virus (IBDV) is a serine protease that processes the polyprotein for viral assembly. VP4 has been found to associate primarily with type II IBDV tubules that are 24 nm in diameter. In this study, a chimeric VP4, assigned as HS1VP4, was constructed with a VP4-autocleavage site inserted between the N-terminal His-tag and the VP4 sequence. The results showed that the VP4 forms tubules after the self-cleavage of HS1VP4 when expressed in Escherichia coli. Furthermore, a deletion of 28 amino acids at the C-terminus of VP4 resulted in monomers and dimers instead of tubule formation; mutants of S652A and K692A at active site destroyed the activity. The endopeptidase activity of these monomers and dimers was approximately 12.5 times higher than that of VP4 tubules. Additionally, the formation of tubules inhibited VP4 protease activity, as demonstrated through in vitro assays. The production and characterization of monomers or dimers that have greater endopeptidase activity and protease activity than tubules can provide further insight into VP4 tubule assembly and the regulation of VP4 activity in host cells; this insight will facilitate the development of new anti-IBDV strategies. 相似文献
36.
Sayali C. Ranade Sarfaraz Nawaz Arnab Chakrabarti Pierre Gressens Shyamala Mani 《Hormones and behavior》2013
"The goal of this study was to examine the effect of maternal iron deficiency on the developing hippocampus in order to define a developmental window for this effect, and to see whether iron deficiency causes changes in glucocorticoid levels. The study was carried out using pre-natal, post-natal, and pre + post-natal iron deficiency paradigm. Iron deficient pregnant dams and their pups displayed elevated corticosterone which, in turn, differentially affected glucocorticoid receptor (GR) expression in the CA1 and the dentate gyrus. Brain Derived Neurotrophic Factor (BDNF) was reduced in the hippocampi of pups following elevated corticosterone levels. Reduced neurogenesis at P7 was seen in pups born to iron deficient mothers, and these pups had reduced numbers of hippocampal pyramidal and granule cells as adults. Hippocampal subdivision volumes also were altered. The structural and molecular defects in the pups were correlated with radial arm maze performance; reference memory function was especially affected. Pups from dams that were iron deficient throughout pregnancy and lactation displayed the complete spectrum of defects, while pups from dams that were iron deficient only during pregnancy or during lactation displayed subsets of defects. These findings show that maternal iron deficiency is associated with altered levels of corticosterone and GR expression, and with spatial memory deficits in their pups." 相似文献
37.
38.
Venkat R. Gadhachanda Kyle J. Eastman Qiuping Wang Avinash S. Phadke Dharaben Patel Wengang Yang Christopher W. Marlor Milind Deshpande Mingjun Huang Jason A. Wiles 《Bioorganic & medicinal chemistry letters》2018,28(21):3463-3471
An unprecedented series of organometallic HCV (hepatitis C virus) NS5A (nonstructural 5A protein) replication complex inhibitors that incorporates a 1,1′-ferrocenediyl scaffold was explored. This scaffold introduces the elements of linear flexibility and non-planar topology that are unconventional for this class of inhibitors. Data from 2-D NMR spectroscopic analyses of these complexes in solution support an anti (unstacked) arrangement of the pharmacophoric groups. Several complexes demonstrate single-digit picomolar in vitro activity in an HCV genotype-1b replicon system. One complex to arise from this investigation (10a) exhibits exceptional picomolar activity against HCV genotype 1a and 1b replicons, low hepatocellular cytotoxicity, and good pharmacokinetic properties in rat. 相似文献
39.
系统调查沟眶象Eucryptorrhynchus chinensis(Olivier)在宁夏灵武市的发生情况和特点发现:沟眶象以成虫和幼虫在土壤中越冬,成虫有2个发生高峰期,越冬结束后以成虫越冬的沟眶象出土出现第1个高峰期,以幼虫越冬的沟眶象经化蛹羽化出土出现第2个高峰期;幼虫危害臭椿根部形成的瘤状物可以作为鉴别沟眶象危害的特征;沟眶象幼虫在土壤中垂直分布范围集中在0~45 cm深土层,约占80%;成虫出土孔集中在距臭椿树干基部75 cm范围内,占88%。据此建议土壤施药化学防治沟眶象时,施药深度不宜低于45 cm,施药点距树干基部水平距离不得少于75 cm,且树周各个方向均需施药。每年10月末沟眶象开始"入土"、翌年4月末开始"出土",在沟眶象"入土"结束后但未冻土之前的11中旬和土壤解冻之后但尚未"出土"前的4月中旬,这两个时期土壤施药防治效果较好;防治沟眶象的同时,还应适时采取打孔注药、熏蒸等措施防治臭椿(Ailanthus altissima(Mill.)Swingle)树干内的臭椿沟眶象Eucryptorrhynchus brandti(Harold)。 相似文献
40.
Joseph A. Jurcisek Amanda C. Dickson Molly E. Bruggeman Lauren O. Bakaletz 《Journal of visualized experiments : JoVE》2011,(47)
The chronic nature of many diseases is attributed to the formation of bacterial biofilms which are recalcitrant to traditional antibiotic therapy. Biofilms are community-associated bacteria attached to a surface and encased in a matrix. The role of the extracellular matrix is multifaceted, including facilitating nutrient acquisition, and offers significant protection against environmental stresses (e.g. host immune responses). In an effort to acquire a better understanding as to how the bacteria within a biofilm respond to environmental stresses we have used a protocol wherein we visualize bacterial biofilms which have formed in an 8-well chamber slide. The biofilms were stained with the BacLight Live/Dead stain and examined using a confocal microscope to characterize the relative biofilm size, and structure under varying incubation conditions. Z-stack images were collected via confocal microscopy and analyzed by COMSTAT. This protocol can be used to help elucidate the mechanism and kinetics by which biofilms form, as well as identify components that are important to biofilm structure and stability. 相似文献