全文获取类型
收费全文 | 2818篇 |
免费 | 229篇 |
国内免费 | 1篇 |
出版年
2023年 | 16篇 |
2022年 | 41篇 |
2021年 | 67篇 |
2020年 | 49篇 |
2019年 | 54篇 |
2018年 | 80篇 |
2017年 | 70篇 |
2016年 | 94篇 |
2015年 | 118篇 |
2014年 | 141篇 |
2013年 | 182篇 |
2012年 | 215篇 |
2011年 | 213篇 |
2010年 | 133篇 |
2009年 | 111篇 |
2008年 | 133篇 |
2007年 | 132篇 |
2006年 | 141篇 |
2005年 | 113篇 |
2004年 | 110篇 |
2003年 | 68篇 |
2002年 | 71篇 |
2001年 | 63篇 |
2000年 | 40篇 |
1999年 | 44篇 |
1998年 | 20篇 |
1997年 | 30篇 |
1996年 | 24篇 |
1995年 | 27篇 |
1994年 | 14篇 |
1993年 | 12篇 |
1992年 | 32篇 |
1991年 | 27篇 |
1990年 | 27篇 |
1989年 | 22篇 |
1988年 | 24篇 |
1987年 | 18篇 |
1986年 | 17篇 |
1985年 | 25篇 |
1984年 | 22篇 |
1983年 | 16篇 |
1982年 | 30篇 |
1981年 | 14篇 |
1980年 | 19篇 |
1979年 | 18篇 |
1977年 | 20篇 |
1974年 | 12篇 |
1973年 | 10篇 |
1972年 | 12篇 |
1967年 | 11篇 |
排序方式: 共有3048条查询结果,搜索用时 15 毫秒
1.
Background
Substituted catechols are important precursors for large-scale synthesis of pharmaceuticals and other industrial products. Most of the reported chemical synthesis methods are expensive and insufficient at industrial level. However, biological processes for production of substituted catechols could be highly selective and suitable for industrial purposes. 相似文献2.
3.
Metal ionophores are considered as potential anti-dementia agents, and some are currently undergoing clinical trials. Many metals are known to accumulate and distribute abnormally in the aging brain. Alterations in zinc metal homeostasis in the glutaminergic synapse could contribute to ageing and the pathophysiology of Alzheimer’s disease (AD). The present study was designed to investigate the effect of metal ionophores on long term administration of zinc in D-galactose induced senescent mice. The ageing model was established by combined administration of zinc and D-galactose to mice for 6 weeks. A novel metal ionophore, PBT-2 was given daily to zinc-induced d-galactose senescent mice. The cognitive behaviour of mice was monitored using the Morris Water Maze. The anti-oxidant status and amyloidogenic activity in the ageing mouse was measured by determining mito-oxidative parameters and deposition of amyloid β (Aβ) in the brain. Systemic administration of both zinc and D-galactose significantly produced memory deficits, mito-oxidative damage, heightened acetylcholinesterase enzymatic activity and deposition of amyloid-β. Treatment with PBT-2 significantly improved behavioural deficits, biochemical profiles, cellular damage, and curbed the deposition of APP in zinc-induced senescent mice. These findings suggest that PBT-2, acting as a metal protein attenuating compound, may be helpful in the prevention of AD or alleviation of ageing. 相似文献
4.
The RAD6 gene of Saccharomyces cerevisiae, which encodes a ubiquitin-conjugating enzyme, is required for DNA repair, DNA damage-induced mutagenesis and sporulation. To evaluate the biological relevance of the thioester adduct between RAD6 protein and ubiquitin, formed as an obligatory, transient intermediate during ubiquitin conjugation to substrates, we altered cysteine 88 in RAD6 to serine. Esterification with ubiquitin occurs at serine 88 in the mutant protein, but conjugation of ubiquitin to the test substrate histone H2A is inactivated. Phenotypically, strains harboring the rad6 Ser88 allele are indistinguishable from rad6 deletion (rad6 delta) mutant cells. These findings argue against ligation of ubiquitin at cysteine 88 acting as a functional switch of a cryptic biochemical activity in RAD6. 相似文献
5.
6.
Escherichia coli strain CAN is unable to support the growth of bacteriophage T4 strains requiring the suppressor function of T4 tRNASer. Biochemical analysis of the mutant strain revealed that it is deficient in a RNase which acts on the artificial tRNA precursor tRNA-C-U. 相似文献
7.
Prakash M. Nadkarni 《Genomics》1995,30(3)
A consensus framework map of a chromosome is the single most useful map of the chromosome, because of the amount of information it holds as well as the quality of the supporting data backing the putative order of its objects. We describe data structures and algorithms to assist in framework map maintenance and to answer queries about order and distance on genomic objects. We show how these algorithms are efficiently implemented in a client-server relational database. We believe that our data structures are particularly suitable for databases to support collaborative mapping efforts that use heterogeneous methodologies. We summarize two applications that use these algorithms: CHROMINFO, a database specifically designed for framework map maintenance; and the shared client-server database for the chromosome 12 genome center. 相似文献
8.
Prakash Bhuta Stanislav Chládek 《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1982,698(2):167-172
The effect of the antibiotics thiostrepton and micrococcin on EF-Tu-catalyzed (ribosome-dependent) GTP hydrolysis in the presence of A-Phe, C-A-Phe, or C-C-A-Phe (related to the sequence of the 3′-terminus of aminoacyl-tRNA)(System I) or by methanol (‘uncoupled GTPase’, System II) was investigated. In System I, thiostrepton increases the binding affinities of the effectors to the EF-Tu·GTP·70 S ribosome complex, as well as the extent of the GTP hydrolysis, while the KGTPm is virtually unchanged. Similarly, in the uncoupled system (System II) and in the absence of effectors, thiostrepton significantly increases VGTPmax, whereas KGTPm remains unaffected. Micrococcin is without any effect in both systems. The ‘uncoupled GTPase’ (in System II) is also strongly inhibited by C-A-Phe. The results indicate the crucial role of the EF-Tu site which binds the aminoacylated C-C-A terminus of aminoacyl-tRNA in promoting GTP hydrolysis. It follows that the binding of the model effectors (such as C-C-A-Phe) to that site is favorably influenced by the interaction of thiostrepton with the 50 S ribosomal subunit, whereas thiostrepton, per se, does not influence the affinity of EF-Tu for GTP. 相似文献
9.
10.
Alzheimer's disease (AD) is a severe age dependent and chronic problem with no cure so far. The available treatments are temporary, acting over short period of time. The main pathological hallmark of the disease includes cholinergic dysfunction, oxidative stress, accumulation of Aβ fibrils and tau tangles. In context with the multi-factorial nature of this disease, two different series of molecules were developed to hit the multifactorial disease targets. Mainly, the molecules were designed to inhibit the AChE and aggregation of Aβ, and also oxidative damage. Two novel series of TAC-fenbufen/menbutone conjugated molecules were designed, synthesized and bio-assayed. All compounds showed inhibition capacity towards AChE, Aβ aggregation and moderate to good radical scavenging capacity. Particularly, five TAC-menbutone molecules showed improved AChE and Aβ aggregation inhibition capacity compared to TAC-fenbufen conjugated molecules. Overall, these novel series of molecules may be potential drug lead molecules in the treatment of AD. 相似文献