全文获取类型
收费全文 | 292篇 |
免费 | 21篇 |
国内免费 | 9篇 |
出版年
2022年 | 2篇 |
2021年 | 5篇 |
2019年 | 7篇 |
2018年 | 2篇 |
2017年 | 3篇 |
2016年 | 4篇 |
2015年 | 16篇 |
2014年 | 11篇 |
2013年 | 12篇 |
2012年 | 16篇 |
2011年 | 19篇 |
2010年 | 13篇 |
2009年 | 12篇 |
2008年 | 19篇 |
2007年 | 10篇 |
2006年 | 11篇 |
2005年 | 7篇 |
2004年 | 13篇 |
2003年 | 4篇 |
2002年 | 9篇 |
2001年 | 8篇 |
2000年 | 7篇 |
1999年 | 5篇 |
1998年 | 8篇 |
1997年 | 11篇 |
1996年 | 8篇 |
1995年 | 3篇 |
1994年 | 7篇 |
1993年 | 2篇 |
1992年 | 6篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 5篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 2篇 |
1983年 | 2篇 |
1982年 | 5篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1977年 | 3篇 |
1975年 | 4篇 |
1971年 | 1篇 |
1968年 | 2篇 |
1967年 | 3篇 |
1966年 | 1篇 |
1960年 | 2篇 |
1955年 | 1篇 |
1954年 | 2篇 |
排序方式: 共有322条查询结果,搜索用时 15 毫秒
91.
DNA topoisomerase II (Top2) is an essential nuclear enzyme and a target of very effective anticancer drugs including anthracycline antibiotics. Even though several aspects of drug activity against Top2 are understood, the drug receptor site is not yet known. Several Top2 mutants have altered drug sensitivity and have provided information of structural features determining drug action. Here, we have investigated the sensitivity to three closely related anthracycline derivatives of yeast Top2 bearing mutations in the CAP-like domain and integrated the findings with computer models of ternary drug-enzyme-DNA complexes. The results suggest a model for the anthracycline receptor wherein a drug molecule has specific interactions with the cleaved DNA as well as amino acid residues of the CAP-like domain of an enzyme monomer. The drug molecule is intercalated into DNA at the site of cleavage, and interestingly, drug-enzyme contacts involve one side of the four-ring chromophore and the side chain of the anthracycline molecule. The findings may explain several established structure-activity relationships of antitumor anthracyclines and may thus provide a framework for further developments of effective Top2 poisons. 相似文献
92.
比较了不同季节和冬眠时相中达乌尔黄鼠 (Citelleusdauricus)下丘脑内去甲肾上腺素 (noradrenaline ,NA)代谢和视前区 (POA)脑片中各类温敏神经元的比例、温度敏感性、放电活动的临界温度及下限温度 .结果表明 :与夏季动物相比 ,( 1)冬眠各时相中POA温敏神经元的比例和温敏性产生了与冬眠体温调节特性相关的适应性改变 ;( 2 )冬季和冬眠中POA神经元放电的下限温度和温敏神经元活动的临界温度均显著下移 ;( 3 )冬眠中POA神经元对NA反应的敏感性增高 ,冷敏神经元对NA的反应从夏季的抑制型转变为冬眠时的兴奋型 ;( 4)入眠和深冬眠时下丘脑内NA的含量和代谢水平下降 ,出眠时代谢水平升高 .这些变化可能解释动物入眠时主动降低体温和出眠时从深低体温中快速地升温的温度调节机理 . 相似文献
93.
Substitution bias, rapid saturation, and the use of mtDNA for nematode systematics 总被引:13,自引:0,他引:13
Only relatively recently have researchers turned to molecular methods for
nematode phylogeny reconstruction. Thus, we lack the extensive literature
on evolutionary patterns and phylogenetic usefulness of different DNA
regions for nematodes that exists for other taxa. Here, we examine the
usefulness of mtDNA for nematode phylogeny reconstruction and provide data
that can be used for a priori character weighting or for parameter
specification in models of sequence evolution. We estimated the
substitution pattern for the mitochondrial ND4 gene from intraspecific
comparisons in four species of parasitic nematodes from the family
Trichostrongylidae (38-50 sequences per species). The resulting pattern
suggests a strong mutational bias toward A and T, and a lower
transition/transversion ratio than is typically observed in other taxa. We
also present information on the relative rates of substitution at first,
second, and third codon positions and on relative rates of saturation of
different types of substitutions in comparisons ranging from intraspecific
to interordinal. Silent sites saturate extremely quickly, presumably owing
to the substitution bias and, perhaps, to an accelerated mutation rate.
Results emphasize the importance of using only the most closely related
sequences in order to infer patterns of substitution accurately for
nematodes or for other taxa having strongly composition-biased DNA. ND4
also shows high amino acid polymorphism at both the intra- and
interspecific levels, and in higher level comparisons, there is evidence of
saturation at variable amino acid sites. In general, we recommend using
mtDNA coding genes only for phylogenetics of relatively closely related
nematode species and, even then, using only nonsynonymous substitutions and
the more conserved mitochondrial genes (e.g., cytochrome oxidases). On the
other hand, the high substitution rate in genes such as ND4 should make
them excellent for population genetics studies, identifying cryptic
species, and resolving relationships among closely related congeners when
other markers show insufficient variation.
相似文献
94.
Fucose is a major constituent of the protein- and lipid-linked glycans of
the various life-cycle stages of schistosomes. These fucosylated glycans
are highly antigenic and seem to play a role in the pathology of
schistosomiasis. In this article we describe the identification and
characterization of two fucosyltransferases (FucTs) in cercariae of the
avian schistosome Trichobilharzia ocellata, a GDP-Fuc:[Galbeta1--
>4]GlcNAcbeta-R alpha1-->3-FucT and a novel GDP-Fuc:Fucalpha-R
alpha1-- >2-FucT. Triton X-100 extracts of cercariae were assayed for
FucT activity using a variety of acceptor substrates. Type 1 chain
(Galbeta1- ->3GlcNAc) based compounds were poor acceptors, whereas those
based on a type 2 chain (Galbeta1-->4GlcNAc), whether
alpha2'-fucosylated, alpha3'-sialylated, or unsubstituted, and whether
present as oligosaccharide or contained in a glycopeptide or glycoprotein,
all served as acceptor substrates. In this respect the schistosomal alpha3-
FucT resembles human FucT V and VI rather than other known FucTs. N-
ethylmaleimide, an inhibitor of several human FucTs, had no effect on the
activity of the schistosomal alpha3-FucT, whereas GDP-beta-S was strongly
inhibitory. Large scale incubations were carried out with
Galbeta1-->4GlcNAc, GalNAcbeta1-->4GlcNAcbeta-O -(CH2)8COOCH3 and
Fucalpha1-->3GlcNAcbeta1-->2Man as acceptor substrates and the
products of the incubations were isolated using a sequence of
chromatographic techniques. By methylation analysis and 2D-TOCSY and
ROESY1H-NMR spectroscopy the products formed were shown to be Galbeta1--
>4[Fucalpha1-->2Fucalpha1-->3]GlcNAc,
GalNAcbeta1-->4[Fucalpha1-- >2Fucalpha1-->3]GlcNAcbe
ta-O-(CH2)8COOCH3, and Fucalpha1-->2Fucalpha1--
>3GlcNAcbeta1-->2Man, respectively. It is concluded that the alpha2-
FucT and alpha3-FucT are involved in the biosynthesis of the (oligomeric)
Lewisx sequences and the Fucalpha1-->2Fucalpha1-->3GlcNAc structural
element that have been described on schistosomal glycoconjugates.
相似文献
95.
Patterns of distribution and abundance of coral reef fish depend in part on recruitment of a pelagic larval stage, on subsequent dispersal among habitats, and survival of new recruits. We studied recruitment of five species of Stegastes and two species of Chromis damselfish onto reef habitats of St. Thomas, USVI during one year. The two study sites, Flat Cay and Outer Brass Island, were on the southern and northern sides of St. Thomas, respectively. At both sites, recruitment occurred largely in the summer months, although one species (Stegastes planifrons) showed significant winter recruitment at Flat Cay. The onset of increased summer recruitment in 1992 of other species occurred several weeks later and was shorter in duration at Outer Brass Island than at Flat Cay, perhaps indicating differences in oceanographic conditions (currents etc.) or spawning cycles between sites. The two Chromis species showed lunar periodicity of settlement at Flat Cay. At Flat Cay, recruits of three species (S. leucostictus, S. diencaeus and S. planifrons) were associated with conspecifics possibly due to preferential settlement. Similarly, new recruits were more often found near live coral than coral rubble, and very few occurred on sand habitat. Substratum complexity was a poor predictor of recruitment within a habitat, although larger juveniles of some species were more common on more complex substrate. Contrary to other studies, there were no apparent depth preferences among recruits, although larger juveniles of two Stegastes species were found more often in deeper water. It appears that within habitats, newly arriving larvae may be attracted first to the presence of conspecifics and secondarily take up position adjacent to live coral. Apparent survivorship of some Stegastes species and one Chromis species was higher at Outer Brass Island than at Flat Cay, and may partly compensate for lower recruitment of some species at Outer Brass Island. 相似文献
96.
97.
98.
99.
Orioli M Aldini G Beretta G Facino RM Carini M 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2005,827(1):109-118
A sensitive, selective, specific and rapid liquid chromatographic-electrospray ionization tandem mass spectrometric assay was developed and validated for the simultaneous determination in skeletal muscle of the Michael adducts between 4-hydroxy-trans-2-nonenal (HNE), one of the most reactive lipid peroxidation-driven unsaturated aldehyde, and glutathione (GSH) and the endogenous histidine-containing dipeptides carnosine (CAR) and anserine (ANS), with the final aim to use conjugated adducts as specific and unequivocal markers of lipid peroxidation. Samples (skeletal muscle homogenates from male rats) were prepared by protein precipitation with 1 vol. of a HClO(4) solution (4.2%; w/v) containing H-Tyr-His-OH as internal standard. The supernatant, diluted (1:1, v/v) in mobile phase, was separated on a Phenomenex Sinergy polar-RP column with a mobile phase of water-acetonitrile-heptafluorobutyric acid (9:1:0.01, v/v/v) at a flow rate of 0.2 ml/min, with a run time of 12 min. Detection was on a triple quadrupole mass spectrometer equipped with an ESI interface operating in positive ionization mode. The acquisitions were in multiple reaction monitoring (MRM) mode using the following precursor-->product ion combinations: H-Tyr-His-OH (IS): m/z 319.2--> 156.5+301.6; GS-HNE: m/z 464.3--> 179.1+308.0; CAR-HNE: m/z 383.1--> 110.1+266.6; ANS-HNE: m/z 397.2--> 109.1+126.1. The method was validated over the concentration ranges 1.5-90 (GS-HNE) and 0.4-40 (CAR-HNE, ANS-HNE) nmoles/g wet tissue, and the LLOQ were 1.25 and 0.33 pmoles injected respectively. The intra- and inter-day precisions (CV%) were <7.38% (相似文献
100.
Multiphoton fluorescence microscopy has now become a relatively common tool among biophysicists and biologists. The intrinsic sectioning achievable by multiphoton excitation provides a simple means to excite a small volume inside cells and tissues. Multiphoton microscopes have a simplified optical path in the emission side due to the lack of an emission pinhole, which is necessary with normal confocal microscopes. This article illustrates examples in which this advantage in the simplified optics is exploited to achieve a new type of measurements. First, dual-emission wavelength measurements are used to identify regions of different phase domains in giant vesicles and to perform fluctuation experiments at specific locations in the membrane. Second, we show how dual-wavelength measurements are used in conjunction with scanning fluctuation analysis to measure the changes in the geometry of the domains and the incipient formation of gel domains when the temperature of the giant vesicles is gradually lowered. 相似文献