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   24804篇
  免费   2291篇
  国内免费   1772篇
  2024年   59篇
  2023年   638篇
  2022年   832篇
  2021年   1230篇
  2020年   1098篇
  2019年   1291篇
  2018年   1171篇
  2017年   1024篇
  2016年   1117篇
  2015年   1251篇
  2014年   1571篇
  2013年   2006篇
  2012年   1139篇
  2011年   1327篇
  2010年   966篇
  2009年   1189篇
  2008年   1210篇
  2007年   1129篇
  2006年   1097篇
  2005年   964篇
  2004年   912篇
  2003年   710篇
  2002年   713篇
  2001年   560篇
  2000年   433篇
  1999年   397篇
  1998年   379篇
  1997年   335篇
  1996年   248篇
  1995年   244篇
  1994年   267篇
  1993年   177篇
  1992年   186篇
  1991年   121篇
  1990年   122篇
  1989年   93篇
  1988年   87篇
  1987年   70篇
  1986年   62篇
  1985年   62篇
  1984年   62篇
  1983年   50篇
  1982年   57篇
  1981年   49篇
  1980年   28篇
  1979年   30篇
  1978年   23篇
  1977年   18篇
  1976年   16篇
  1974年   14篇
排序方式: 共有10000条查询结果,搜索用时 687 毫秒
61.
Assessing the impact of hybrids between transgenic plants and nontarget wild species involves answering several questions such as: (i) what are the hybridization and introgression rates; (ii) what is the behaviour of a transgene in a wild population; and (iii) what will be the consequences of the expression of a transgene in a wild population? These issues are discussed using results from experiments on oilseed rape and wild related Brassiceae. Evidence is given of large variations in the estimates of cross-fertilization probabilities. The first stage of introgression into wild populations is demonstrated to occur spontaneously through back-crossing. Population analysis may also be valuable to detect traces of past introgression. Data from the literature on weed biology, and especially herbicide resistance, are used to illustrate the behaviour of a new gene in weed populations. The need for computer models simulating the introgression process is stressed.  相似文献   
62.
PrPC is associated with a variety of functions, and its ability to interact with a multitude of partners, including itself, may largely explain PrP multifunctionality and the lack of consensus on the genuine physiological function of the protein in vivo. In contrast, there is a consensus in the literature that alterations in PrPC trafficking and intracellular retention result in neuronal degeneration. In addition, a proteolytic modification in the late secretory pathway termed the α-cleavage induces the secretion of PrPN1, a PrPC-derived metabolite with fascinating neuroprotective activity against toxic oligomeric Aβ molecules implicated in Alzheimer disease. Thus, studies focusing on understanding the regulation of PrPC trafficking to the cell surface and the modulation of α-cleavage are essential. The objective of this commentary is to highlight recent evidences that PrPC homodimerization stimulates trafficking of the protein to the cell surface and results in high levels of PrPN1 secretion. We also discuss a hypothetical model for these results and comment on future challenges and opportunities.  相似文献   
63.
《Free radical research》2013,47(6-7):451-462
Abstract

Aging and neurodegenerative diseases share oxidative stress cell damage and depletion of endogenous antioxidants as mechanisms of injury, phenomena that are occurring at different rates in each process. Nevertheless, as the central nervous system (CNS) consists largely of lipids and has a poor catalase activity, a low amount of superoxide dismutase and is rich in iron, its cellular components are damaged easily by overproduction of free radicals in any of these physiological or pathological conditions. Thus, antioxidants are needed to prevent the formation and to oppose the free radicals damage to DNA, lipids, proteins, and other biomolecules. Due to endogenous antioxidant defenses are inadequate to prevent damage completely, different efforts have been undertaken in order to increase the use of natural antioxidants and to develop antioxidants that might ameliorate neural injury by oxidative stress. In this context, natural antioxidants like flavonoids (quercetin, curcumin, luteolin and catechins), magnolol and honokiol are showing to be the efficient inhibitors of the oxidative process and seem to be a better therapeutic option than the traditional ones (vitamins C and E, and β-carotene) in various models of aging and injury in vitro and in vivo conditions. Thus, the goal of the present review is to discuss the molecular basis, mechanisms of action, functions, and targets of flavonoids, magnolol, honokiol and traditional antioxidants with the aim of obtaining better results when they are prescribed on aging and neurodegenerative diseases.  相似文献   
64.
《Phytomedicine》2014,21(5):704-711
Extract of Acanthopanax senticosus harms (EAS) has been shown to have neuroprotective effects on dopaminergic neurons in Parkinson's disease (PD) mice model. α-Synuclein is a key player in the pathogenesis of PD, the elevated level of which is deleterious to dopaminergic neurons, and enhancing its clearance might be a promising strategy for treating PD. To assess the potential of EAS in this regard, we investigated its effect on the SH-SY5Y cells overexpressing wild-type α-synuclein (WT-α-Syn) or A53T mutant α-synuclein (A53T-α-Syn), and the implicated pathway it might mediate. After treatment with EAS, the changes of α-synuclein, caspase-3, parkin, phospho-protein kinase B (Akt), phospho-glycogen synthase kinase 3 beta (GSK3β), and phospho-microtubule-associated protein tau (Tau) in WT-α-Syn or A53T-α-Syn transgenic cells were reverted back to near normal levels, demonstrated by the western blotting and quantitative real-time PCR outcomes. The neuroprotective effects of EAS may be able to protect WT-α-Syn or A53T-α-Syn transgenic SH-SY5Y cells from α-synuclein overexpression and toxicity. Therefore, we speculate that EAS might be a promising candidate for prevention or treatment of α-synuclein-related neurodegenerative disorders such as PD.  相似文献   
65.
《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   
66.
Abstract The 3D gene of foot-and-mouth disease virus encodes the viral RNA dependent RNA polymerase, also called virus infection associated (VIA) antigen, which is the most important serological marker of virus infection. This 3D gene from a serotype Cl virus has been cloned and overexpressed in Escherichia coli under the control of the strong lambda lytic promoters. The resulting 51 kDa recombinant protein has been shown to be immunoreactive with sera from infected animals. After induction of gene expression, an immediate and dramatic arrest of cell DNA synthesis occurs, similar to that produced by genotoxic doses of the drug mitomycin C. This effect does not occur during the production of either a truncated VIA antigen or other related and non-related viral proteins. The inhibition of DNA replication results in a subsequent induction of the host SOS DNA-repair response and in an increase of the mutation frequency in the surviving cells.  相似文献   
67.
A series of thirty (30) thiazole analogs were prepared, characterized by 1H NMR, 13C NMR and EI-MS and evaluated for Acetylcholinesterase and butyrylcholinesterase inhibitory potential. All analogs exhibited varied butyrylcholinesterase inhibitory activity with IC50 value ranging between 1.59 ± 0.01 and 389.25 ± 1.75 μM when compared with the standard eserine (IC50, 0.85 ± 0.0001 μM). Analogs 15, 7, 12, 9, 14, 1, 30 with IC50 values 1.59 ± 0.01, 1.77 ± 0.01, 6.21 ± 0.01, 7.56 ± 0.01, 8.46 ± 0.01, 14.81 ± 0.32 and 16.54 ± 0.21 μM respectively showed excellent inhibitory potential. Seven analogs 15, 20, 19, 24, 28, 30 and 25 exhibited good acetylcholinesterase inhibitory potential with IC50 values 21.3 ± 0.50, 35.3 ± 0.64, 36.6 ± 0.70, 44.81 ± 0.81, 46.36 ± 0.84, 48.2 ± 0.06 and 48.72 ± 0.91 μM respectively. All other analogs also exhibited well to moderate enzyme inhibition. The binding mode of these compounds was confirmed through molecular docking.  相似文献   
68.
69.
《Developmental cell》2022,57(22):2533-2549.e7
  1. Download : Download high-res image (204KB)
  2. Download : Download full-size image
  相似文献   
70.
A field study was carried out for 6 wks to assess, from both an efficiency and economic perspective, the effect of individual and integrated success of feeding and topical applications of two formulations of Bacillus thuringiensis var. israelensis (Bti) in controlling house fly (Musca domestica L.) larvae and adults in poultry houses. There was no significant difference between the 1 g and 2 g L?1 spray applications of Bti. In the absence of spray applications, no significant differences in larval mortalities were observed between the 250 mg and 500 mg kg?1 feed applications. The percentage mortality of larvae accomplished as a result of using a combination of 250 mg kg?1Bti feed and 2 g L?1 spray applications was equivalent to that obtained as a result of combining 500 mg kg?1Bti and 1g L?1 spray applications. Treatment with Bti caused significant reductions in the emergence (up to 74%) of house fly adults compared to the control. The fact that the emergence of adult house flies was affected by Bti treatments implies that Bti has sublethal effects on house fly larvae. The cost–benefit analysis (expressed in terms of mortality of larvae growing) indicated that the most effective combination for house fly larvae and adult house fly emergence control was the 500 mg kg?1 of feed and 2 g L?1 spray application combination that resulted in 67% larval mortality and a 74% decrease in adult house fly emergence. This study presents commercial users with various alternatives for possible combinations of the two Bti formulations.  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