全文获取类型
收费全文 | 2944篇 |
免费 | 230篇 |
国内免费 | 1篇 |
出版年
2023年 | 14篇 |
2022年 | 41篇 |
2021年 | 84篇 |
2020年 | 36篇 |
2019年 | 51篇 |
2018年 | 57篇 |
2017年 | 60篇 |
2016年 | 99篇 |
2015年 | 176篇 |
2014年 | 172篇 |
2013年 | 204篇 |
2012年 | 281篇 |
2011年 | 260篇 |
2010年 | 143篇 |
2009年 | 145篇 |
2008年 | 180篇 |
2007年 | 181篇 |
2006年 | 175篇 |
2005年 | 145篇 |
2004年 | 140篇 |
2003年 | 131篇 |
2002年 | 122篇 |
2001年 | 18篇 |
2000年 | 14篇 |
1999年 | 22篇 |
1998年 | 21篇 |
1997年 | 17篇 |
1996年 | 13篇 |
1995年 | 13篇 |
1994年 | 17篇 |
1993年 | 15篇 |
1992年 | 15篇 |
1991年 | 11篇 |
1990年 | 9篇 |
1989年 | 7篇 |
1988年 | 11篇 |
1987年 | 6篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 7篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 6篇 |
1974年 | 2篇 |
1973年 | 6篇 |
1972年 | 3篇 |
1971年 | 4篇 |
排序方式: 共有3175条查询结果,搜索用时 437 毫秒
111.
Anja Be
Marija Mio
Branimir Bertoa Marija Kos Patricia Debogovi Marijeta Kralj Kristina Star
evi Marijana Hranjec 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1327
As a result of our previous research focussed on benzimidazoles, herein we present design, synthesis, QSAR analysis and biological activity of novel N-substituted benzimidazole derived carboxamides. Carboxamides were designed to study the influence of the number of methoxy groups, the type of the substituent placed at the benzimidazole core on biological activity. Pronounced antioxidative activity displayed unsubstituted 28 (IC50 ≈ 3.78 mM, 538.81 mmolFe2+/mmolC) and dimethoxy substituted derivative 34 (IC50 ≈ 5.68 mM, 618.10 mmolFe2+/mmolC). Trimethoxy substituted 43 and unsubstituted compound 40 with isobutyl side chain at N atom showed strong activity against HCT116 (IC50 ≈ 0.6 µM, both) and H 460 cells (IC50 ≈ 2.5 µM; 0.4 µM), being less cytotoxic towards non-tumour cell. Antioxidative activity in cell generally confirmed relatively modest antioxidant capacity obtained in DPPH/FRAP assays of derivatives 34 and 40. The 3D-QSAR models were generated to explore molecular properties that have the highest influence on antioxidative activity. 相似文献
112.
113.
114.
115.
To examine the relationship between gene conversion and reciprocal exchange at an endogenous chromosomal locus, we developed a reversion assay in a thymidine kinase deficient mutant, TX545, derived from the human lymphoblastoid cell line TK6. Selectable revertants of TX545 can be generated through interchromosomal gene conversion at the site of inactivating mutations on each tk allele or by reciprocal exchange that alters the linkage relationships of inactivating polymorphisms within the tk locus. Analysis of loss of heterozygosity (LOH) at intragenic polymorphisms and flanking microsatellite markers was used to initially evaluate allelotypes in TK(+) revertants for patterns associated with either gene conversion or crossing over. The linkage pattern in a subset of convertants was then unambiguously established, even in the event of prereplicative recombinational exchanges, by haplotype analysis of flanking microsatellite loci in tk(-/-) LOH mutants collected from the tk(+/-) parental convertant. Some (7/38; 18%) revertants were attributable to easily discriminated nonrecombinational mechanisms, including suppressor mutations within the tk coding sequence. However, all revertants classified as a recombinational event (28/38; 74%) were attributed to localized gene conversion, representing a highly significant preference (P < 0.0001) over gene conversion with associated reciprocal exchange, which was never observed. 相似文献
116.
Placental failure and impaired vasculogenesis result in embryonic lethality for neuropathy target esterase-deficient mice 总被引:8,自引:0,他引:8 下载免费PDF全文
Moser M Li Y Vaupel K Kretzschmar D Kluge R Glynn P Buettner R 《Molecular and cellular biology》2004,24(4):1667-1679
Age-dependent neurodegeneration resulting from widespread apoptosis of neurons and glia characterize the Drosophila Swiss Cheese (SWS) mutant. Neuropathy target esterase (NTE), the vertebrate homologue of SWS, reacts with organophosphates which initiate a syndrome of axonal degeneration. NTE is expressed in neurons and a variety of nonneuronal cell types in adults and fetal mice. To investigate the physiological functions of NTE, we inactivated its gene by targeted mutagenesis in embryonic stem cells. Heterozygous NTE(+/-) mice displayed a 50% reduction in NTE activity but underwent normal organ development. Complete inactivation of the NTE gene resulted in embryonic lethality, which became evident after gastrulation at embryonic day 9 postcoitum (E9). As early as E7.5, mutant embryos revealed growth retardation which did not reflect impaired cell proliferation but rather resulted from failed placental development; as a consequence, massive apoptosis within the developing embryo preceded its resorption. Histological analysis indicated that NTE is essential for the formation of the labyrinth layer and survival and differentiation of secondary giant cells. Additionally, impairment of vasculogenesis in the yolk sacs and embryos of null mutant conceptuses suggested that NTE is also required for normal blood vessel development. 相似文献
117.
Observations in enrichment cultures of ferric iron-reducing bacteria indicated that ferrihydrite was reduced to ferrous iron minerals via sulfur cycling with sulfide as the reductant. Ferric iron reduction via sulfur cycling was investigated in more detail with Sulfurospirillum deleyianum, which can utilize sulfur or thiosulfate as an electron acceptor. In the presence of cysteine (0.5 or 2 mM) as the sole sulfur source, no (microbial) reduction of ferrihydrite or ferric citrate was observed, indicating that S. deleyianum is unable to use ferric iron as an immediate electron acceptor. However, with thiosulfate at a low concentration (0.05 mM), growth with ferrihydrite (6 mM) was possible and sulfur was cycled up to 60 times. Also, spatially distant ferrihydrite in agar cultures was reduced via diffusible sulfur species. Due to the low concentrations of thiosulfate, S. deleyianum produced only small amounts of sulfide. Obviously, sulfide delivered electrons to ferrihydrite with no or only little precipitation of black iron sulfides. Ferrous iron and oxidized sulfur species were produced instead, and the latter served again as the electron acceptor. These oxidized sulfur species have not yet been identified. However, sulfate and sulfite cannot be major products of ferrihydrite-dependent sulfide oxidation, since neither compound can serve as an electron acceptor for S. deleyianum. Instead, sulfur (elemental S or polysulfides) and/or thiosulfate as oxidized products could complete a sulfur cycle-mediated reduction of ferrihydrite. 相似文献
118.
119.
Lai CM Yu MJ Brankov M Barnett NL Zhou X Redmond TM Narfstrom K Rakoczy PE 《Genetic vaccines and therapy》2004,2(1):3
Background
Leber's congenital amaurosis (LCA) is a severe form of retinal dystrophy. Mutations in the RPE65 gene, which is abundantly expressed in retinal pigment epithelial (RPE) cells, account for approximately 10–15% of LCA cases. In this study we used the high turnover, and rapid breeding and maturation time of the Rpe65 -/- knockout mice to assess the efficacy of using rAAV-mediated gene therapy to replace the disrupted RPE65 gene. The potential for rAAV-mediated gene treatment of LCA was then analyzed by determining the pattern of RPE65 expression, the physiological and histological effects that it produced, and any improvement in visual function. 相似文献120.
Gruden K Kuipers AG Guncar G Slapar N Strukelj B Jongsma MA 《Insect biochemistry and molecular biology》2004,34(4):365-375
Potato synthesises high levels of proteinase inhibitors in response to insect attack. This can adversely affect protein digestion in the insects, leading to reduced growth, delayed development and lowered fecundity. Colorado potato beetle overcomes this defence mechanism by changing the composition of its digestive proteinases. The induced cysteine proteinases in the adapted gut sustain a normal rate of protein hydrolysis either by inactivating the inhibitors by cleavage or by insensitivity to the inhibitors as a result of high Kis. In this study cDNA clones of cysteine proteinases in adapted guts were isolated by nested PCR on the basis of N-terminal sequences previously determined for purified enzymes (Gruden et al., 2003). The cysteine proteinase cDNAs can be classified into three groups: intestains A, B and C. The amino acid identity is more than 91% within and 35-62% between the groups. They share 43-50% identity to mammalian cathepsins S, L, K, H, J and cathepsin-like enzymes from different arthropods. Homology modelling predicts that intestains A, B and C follow the general fold of papain-like proteinases. Intestains from each group, however, differ in some specific structural characteristics in the S1 and S2 binding sites that could influence enzyme-inhibitor interaction and thus, provide different mechanisms of resistance to inhibitors for the different enzymes. Gene expression analysis revealed that the intestains A and C, but not B, are induced twofold by potato plants with high levels of proteinase inhibitors. 相似文献