全文获取类型
收费全文 | 555篇 |
免费 | 9篇 |
出版年
2021年 | 5篇 |
2019年 | 4篇 |
2018年 | 7篇 |
2017年 | 13篇 |
2016年 | 8篇 |
2015年 | 6篇 |
2014年 | 7篇 |
2013年 | 18篇 |
2012年 | 21篇 |
2011年 | 22篇 |
2010年 | 16篇 |
2009年 | 13篇 |
2008年 | 29篇 |
2007年 | 21篇 |
2006年 | 20篇 |
2005年 | 16篇 |
2004年 | 18篇 |
2003年 | 13篇 |
2002年 | 15篇 |
2001年 | 10篇 |
2000年 | 16篇 |
1999年 | 8篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1992年 | 9篇 |
1991年 | 9篇 |
1990年 | 12篇 |
1989年 | 15篇 |
1988年 | 20篇 |
1987年 | 15篇 |
1986年 | 12篇 |
1985年 | 18篇 |
1984年 | 10篇 |
1983年 | 7篇 |
1982年 | 4篇 |
1979年 | 5篇 |
1978年 | 6篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1975年 | 10篇 |
1974年 | 15篇 |
1973年 | 13篇 |
1972年 | 5篇 |
1971年 | 9篇 |
1970年 | 9篇 |
1969年 | 4篇 |
1968年 | 6篇 |
1967年 | 8篇 |
1966年 | 4篇 |
1965年 | 4篇 |
排序方式: 共有564条查询结果,搜索用时 446 毫秒
101.
Hsin-Yu Lee Radu M. Suciu Benjamin D. Horning Ekaterina V. Vinogradova Olesya A. Ulanovskaya Benjamin F. Cravatt 《Bioorganic & medicinal chemistry letters》2018,28(16):2682-2687
Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation of nicotinamide using S-adenosyl-L-methionine (SAM) as a methyl donor and, through doing so, can modulate cellular methylation potential to impact diverse epigenetic processes. NNMT has been implicated in a range of diseases, including cancer and metabolic disorders. Potent, selective, and cell-active inhibitors would constitute valuable probes to study the biological functions and therapeutic potential of NNMT. We previously reported the discovery of electrophilic small molecules that inhibit NNMT by reacting with an active-site cysteine residue in the SAM-binding pocket. Here, we have used activity-based protein profiling (ABPP)-guided medicinal chemistry to optimize the potency and selectivity of NNMT inhibitors, culminating in the discovery of multiple alpha-chloroacetamide (αCA) compounds with sub-µM IC50 values in vitro and excellent proteomic selectivity in cell lysates. However, these compounds showed much weaker inhibition of NNMT in cells, a feature that was not shared by off-targets of the αCAs. Our results show the potential for developing potent and selective covalent inhibitors of NNMT, but also highlight challenges that may be faced in targeting this enzyme in cellular systems. 相似文献
102.
Yulia Vinogradova Jan Pergl Franz Essl Martin Hejda Mark van Kleunen REGIONAL CONTRIBUTORS Petr Pyšek 《Biological invasions》2018,20(8):1931-1943
Recent research on plant invasions indicates that some parts of the world are understudied with temperate Asia among them. To contribute towards closing this gap, we provide a standardized list of invasive alien plant species with their distributions in 45 Russian regions, and relate the variation in their richness to climate, socioeconomic parameters and human influence. In total, we report 354 invasive alien species. There are, on average, 27 ± 17 (mean ± SD) invasive plants per region, and the invasive species richness varies from zero in Karelia to 71 in Kaluga. In the European part of Russia, there are 277 invasive species in total, in Siberia 70, and in the Far East 79. The most widespread invaders are, in terms of the number of regions from which they are reported, Acer negundo, Echinocystis lobata (recorded in 34 regions), Erigeron canadensis and Elodea canadensis (recorded in 30 regions). Most invasive species in Russia originate from other parts of temperate Asia and Europe. There were significant differences in the representation of life forms between the European, Siberian and Far East biogeographical regions, with perennials being over-represented in the Far East, and shrubs in the European part of Russia. The richness of invasive species can be explained by climatic factors, human population density and the percentage of urban population in a region. This publication and the associated dataset is the first comprehensive treatment of the invasive flora of Russia using standardized criteria and covering 83% of the territory of this country. 相似文献
103.
Thomas GH; Newbern EC; Korte CC; Bales MA; Muse SV; Clark AG; Kiehart DP 《Molecular biology and evolution》1997,14(12):1285-1295
Many structural, signaling, and adhesion molecules contain tandemly
repeated amino acid motifs. The alpha-actinin/spectrin/dystrophin
superfamily of F-actin-crosslinking proteins contains an array of triple
alpha-helical motifs (spectrin repeats). We present here the complete
sequence of the novel beta-spectrin isoform beta(Heavy)- spectrin (beta H).
The sequence of beta H supports the origin of alpha- and beta-spectrins
from a common ancestor, and we present a novel model for the origin of the
spectrins from a homodimeric actin-crosslinking precursor. The pattern of
similarity between the spectrin repeat units indicates that they have
evolved by a series of nested, nonuniform duplications. Furthermore, the
spectrins and dystrophins clearly have common ancestry, yet the repeat unit
is of a different length in each family. Together, these observations
suggest a dynamic period of increase in repeat number accompanied by
homogenization within each array by concerted evolution. However, today,
there is greater similarity of homologous repeats between species than
there is across repeats within species, suggesting that concerted evolution
ceased some time before the arthropod/vertebrate split. We propose a
two-phase model for the evolution of the spectrin repeat arrays in which an
initial phase of concerted evolution is subsequently retarded as each new
protein becomes constrained to a specific length and the repeats diverge at
the DNA level. This evolutionary model has general applicability to the
origins of the many other proteins that have tandemly repeated motifs.
相似文献
104.
Comparisons of the molecular evolutionary process at rbcL and ndhF in the grass family (Poaceae) 总被引:2,自引:1,他引:1
We examine rate heterogeneity among evolutionary lineages of the grass
family at two plasmid loci, ndhF and rbcL, and we introduce a method to
determine whether patterns of rate heterogeneity are correlated between
loci. We show both that rates of synonymous evolution are heterogeneous
among grass lineages and that are heterogeneity is correlated between loci
at synonymous sites. At nonsynonymous sites, the pattern of rate
heterogeneity is not correlated between loci, primarily due to an aberrant
pattern of rate heterogeneity at nonsynonymous sites of rbcL. We compare
patterns of synonymous rate heterogeneity to predictors based on the
generation time effect and the speciation rate hypotheses. Although there
is some evidence for generation time effects, neither generation time
effects nor speciation rates appear to be sufficient to explain patterns of
rate heterogeneity in the grass plastid sequences.
相似文献
105.
Polymorphism of the chromomycin-producing orgnaism Act. aburaviensis var. verrucosus 144--3 was studied. The stable variants differed in the morphologo-cultural properties, assimilation of the carbon sources, the component composition of the luminescence substances and the quantitative property of the antibiotic production. A substance with violet luminescence was found in the culture of varient I in addition to chromomycin. Similarity of the phenotypes observed in variants 1 and 2 when grown on complex organic media is explained by intensive chromomycin production by variant 1 on such media. Active colonies may be selected according to the colour due to chromomycin. Forms with an activity almost 4 times higher than that of the initial culture were found among the colonies of variant 2. 相似文献
106.
107.
A M Nesterov N A Vinogradova N V Kudriavtseva A D Sorkin A B Sorokin 《Tsitologiia》1987,29(9):1020-1026
The increase of uridine phosphorylation during the first hour after epidermal growth factor (EGF) stimulation (1.25 nM) of Swiss 3T3 cells is completely blocked by 100 microM dansylcadaverine (DC). Lack of the effect of DC on uridine transport, uridine kinase activity in cell homogenate, intracellular ATP concentration and plasma membrane permeability for phosphorylated uridine derivatives makes it possible to propose the inhibition by DC (100 microM) of the activated state of uridine kinase. The rapidity of the inhibition of EGF effect and the lack of influence of DC (in tested concentration) upon the clustering of EGF-receptor complexes, rate of their internalization (Sorkin, 1985; Nikol'ski? et al., 1987) and pH value of intracellular compartments (Sorkin et al., 1985; Teslenko et al., 1986) may suggest an association of DC inhibitory action with blocking of some steps of the receptor mediated endocytosis. Accumulation of DC in cell membranes, rather than in intracellular compartments with acidic pH, is a necessary factor for its blocking effect. Possibilities of DC action through the influence on calmodulin-dependent proteins or EGF-induced cell protein phosphorylation are discussed. 相似文献
108.
M N Vinogradova E S Gromova O I Griaznova M G Isaguliants S A Kuznetsova 《Bioorganicheskaia khimiia》1987,13(9):1194-1204
Ability of the EcoRII restriction endonuclease to cleave 14-base-pair DNA duplexes with nucleotide substitutions in the recognition site CCA/TGG and in the adjacent base pair has been studied. Modifications leading to a local change in the substrate conformation (rU residue in and outside the recognition site, A.A- or A.C-pairs in the flanking sequence) reduce the rate of hydrolysis, the effect being maximal when the modified base pair is outside the recognition site. No digestion occurs when the internal dC-residue of the recognition site is 5-methylated in one or both strands. Replacement of dT residue in the EcoRII recognition site by dfl5U residue results in a dramatic inhibition of hydrolysis. Km and kcat for the cleavage of 14-base-pair DNA duplex have been determined. The cleavage rate of the dT-containing strand of the recognition site in 1.5 fold higher comparing with the dA-containing strand. The cleavage of both strands of the substrate by EcoRII endonuclease is confirmed to proceed in one enzyme-substrate complex. 相似文献
109.
110.