全文获取类型
收费全文 | 1032篇 |
免费 | 72篇 |
出版年
2023年 | 4篇 |
2022年 | 12篇 |
2021年 | 29篇 |
2020年 | 11篇 |
2019年 | 14篇 |
2018年 | 23篇 |
2017年 | 21篇 |
2016年 | 33篇 |
2015年 | 52篇 |
2014年 | 64篇 |
2013年 | 87篇 |
2012年 | 77篇 |
2011年 | 74篇 |
2010年 | 52篇 |
2009年 | 43篇 |
2008年 | 49篇 |
2007年 | 78篇 |
2006年 | 66篇 |
2005年 | 55篇 |
2004年 | 33篇 |
2003年 | 42篇 |
2002年 | 42篇 |
2001年 | 12篇 |
2000年 | 5篇 |
1999年 | 15篇 |
1998年 | 9篇 |
1997年 | 7篇 |
1996年 | 3篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 5篇 |
1992年 | 8篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 3篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1973年 | 4篇 |
1972年 | 3篇 |
1970年 | 2篇 |
1969年 | 3篇 |
1961年 | 2篇 |
排序方式: 共有1104条查询结果,搜索用时 31 毫秒
101.
Impairment of cytotype regulation of P-element activity in Drosophila melanogaster by mutations in the Su(var)205 gene 下载免费PDF全文
Cytotype regulation of transposable P elements in the germ line of Drosophila melanogaster is associated with maternal transmission of P elements inserted at the left telomere of the X chromosome. This regulation is impaired in long-term stocks heterozygous for mutations in Suppressor of variegation 205 [Su(var)205], a gene implicated in the control of telomere length. Regulation by TP5, a structurally incomplete P element at the X telomere, is more profoundly impaired than regulation by TP6, a different incomplete P element inserted at the same site in a TAS repeat at the X telomere. Genetic analysis with the TP5 element indicates that its regulatory ability is not impaired in flies whose fathers came directly from a stock heterozygous for a Su(var)205 mutation, even when the flies themselves carry this mutation. However, it is impaired in flies whose grandfathers came from such a stock. Furthermore, this impairment occurs even when the Su(var)205 mutation is not present in the flies themselves or in their mothers. The impaired regulatory ability of TP5 persists for at least several generations after TP5 X chromosomes extracted from a long-term mutant Su(var)205 stock are made homozygous in the absence of the Su(var)205 mutation. Impairment of TP5-mediated regulation is therefore not directly dependent on the Su(var)205 mutation. However, it is characteristic of the six mutant Su(var)205 stocks that were tested and may be related to the elongated telomeres that develop in these stocks. Impairment of regulation by TP5 is also seen in a stock derived from Gaiano, a wild-type strain that has elongated telomeres due to a dominant mutation in the Telomere elongation (Tel) gene. Regulation by TP6 is not impaired in the Gaiano genetic background. The regulatory abilities of the TP5 and TP6 elements are therefore not equally susceptible to the effects of elongated telomeres in the mutant Su(var)205 and Gaiano stocks. 相似文献
102.
We studied the complex formation of tetrakis(4-N-methylpyridyl)porphyrin (TMPyP) with double stranded DNAs and T7 phage nucleoprotein complex. We analyzed the effect of base pair composition of DNA, the presence of capsid protein, and the composition of the microenvironment on the distribution of TMPyP between binding forms as determined by the decomposition of porphyrin absorption spectra. No difference was found in the amount of bound TMPyP between DNAs of various base compositions; however, the ratio of TMPyP binding forms depends on the AT/GC ratio. The presence of protein capsid opposes the binding of TMPyP to DNA. This behavior offers a possibility to investigate the protein capsid integrity due to the analysis of porphyrin binding. Increasing ionic strength of monovalent ions decreases the amount of bound porphyrin through the inhibition of intercalation, but does not influence the quantity of groove-binding forms when TMPyP interacts with isolated DNA. In the case of the nucleoprotein complex the groove-binding is also inhibited already at 140 mM ionic strength. The presence of 1 mM divalent cations (Mg(2+), Ca(2+), Cu(2+) and Ni(2+)) in a buffer solution of 70 mM ionic strength does not influence significantly the free to bound ration of TMPyP when it interacts with isolated DNA. The contribution of binding forms is remarkably different in Mg(2+)/Ca(2+) and Cu(2+)/Ni(2+) containing solutions. Transition metals significantly decrease the binding sites for intercalation in both DNA and nucleoprotein complex, but facilitate the groove-binding of TMPyP to isolated DNA. 相似文献
103.
Perepelov AV Kołodziejska K Kondakova AN Wykrota M Knirel YA Sidorczyk Z Rozalski A 《Carbohydrate research》2004,339(12):2145-2149
On mild acid degradation of the lipopolysaccharide of Proteus vulgaris O34, strain CCUG 4669, the O-polysaccharide was cleaved at a glycosyl-phosphate linkage that is present in the main chain. The resultant phosphorylated oligosaccharides and an alkali-treated lipopolysaccharide were studied by sugar and methylation analyses along with 1H and 13C NMR spectroscopy, and the following structure of the branched tetrasaccharide phosphate repeating unit of the O-polysaccharide was established: [carbohydrate structure: see text]The O-polysaccharide of Proteus mirabilis strain TG 276 was found to have the same structure and, based on the structural and serological data, this strain was proposed to be classified into the same Proteus serogroup O34. 相似文献
104.
P elements inserted near the left telomere of the X chromosome are associated with the P cytotype, a maternally transmitted condition that strongly regulates the activity of the P transposon family in some strains of Drosophila. The regulatory abilities of two such elements, TP5 and TP6, are stable in homozygous stocks over many generations. However, these regulatory abilities are attenuated when the telomeric P elements are transmitted through heterozygous females, and they are utterly lost when the elements are transmitted through males. Paternally transmitted telomeric P elements reacquire regulatory ability when they pass through a female germ line. This reacquisition is enhanced if the females in which it occurs came from mothers who carried a telomeric P element. The enhancement has two components: (1). a strictly maternal effect that is transmitted to the females independently of the mother's telomeric P element ("presetting" or the "pre-P cytotype") and (2). a zygotic effect associated with inheritance of the mother's telomeric P element. One telomeric P element can enhance the reacquisition of another's regulatory ability. When X chromosomes that carry telomeric P elements are extracted through males and made homozygous by using a balancer chromosome, most of the resulting stocks develop strong regulatory abilities in a few generations. However, some of the stocks do not attain the regulatory ability of the original population. 相似文献
105.
Identification and characterization of structural domains of human ERp57: association with calreticulin requires several domains 总被引:1,自引:0,他引:1
Silvennoinen L Myllyharju J Ruoppolo M Orrù S Caterino M Kivirikko KI Koivunen P 《The Journal of biological chemistry》2004,279(14):13607-13615
The amino acid sequence of ERp57, which functions in the endoplasmic reticulum together with the lectins calreticulin and calnexin to achieve folding of newly synthesized glycoproteins, is highly similar to that of protein disulfide isomerase (PDI), but they have their own distinct roles in protein folding. We have characterized the domain structure of ERp57 by limited proteolysis and N-terminal sequencing and have found it to be similar but not identical to that of PDI. ERp57 had three major protease-sensitive regions, the first of which was located between residues 120 and 150, the second between 201 and 215, and the third between 313 and 341, the data thus being consistent with a four-domain structure abb'a'. Recombinant expression in Escherichia coli was used to verify the domain boundaries. Each single domain and a b'a' double domain could be produced in the form of soluble, folded polypeptides, as verified by circular dichroism spectra and urea gradient gel electrophoresis. When the ability of ERp57 and its a and a' domains to fold denatured RNase A was studied by electrospray mass analyses, ERp57 markedly enhanced the folding rate at early time points, although less effectively than PDI, but was an ineffective catalyst of the overall process. The a and a' domains produced only minor, if any, increases in the folding rate at the early stages and no increase at the late stages. Interaction of the soluble ERp57 domains with the P domain of calreticulin was studied by chemical cross-linking in vitro. None of the single ERp57 domains nor the b'a' double domain could be cross-linked to the P domain, whereas cross-linking was obtained with a hybrid ERpabb'PDIa'c polypeptide but not with ERpabPDIb'a'c, indicating that multiple domains are involved in this protein-protein interaction and that the b' domain of ERp57 cannot be replaced by that of PDI. 相似文献
106.
107.
108.
In the yeast Saccharomyces cerevisiae, the Snf1 protein kinase of the Snf1/AMP-activated protein kinase (AMPK) family regulates a wide range of responses to stress caused by glucose deprivation. The stress signal is relayed via upregulation of Snf1, which depends on phosphorylation of its activation loop Thr210 residue by upstream kinases. Although Snf1 is also required for coping with various stresses unrelated to glucose deprivation, some evidence suggests a role for low-level basal activity of unphosphorylated Snf1, rather than a specific signaling function. We previously found that Snf1 is required for diploid pseudohyphal differentiation, a developmental response to nitrogen limitation. Here, we present evidence that Snf1 is directly involved in nitrogen signaling. First, genetic analyses suggest that pseudohyphal differentiation depends on the stimulatory phosphorylation of Snf1 at Thr210. Second, immunochemical data indicate that nitrogen limitation improves Thr210 phosphorylation. Analyses of pseudohyphal differentiation in cells with catalytically inactive and hyperactive Snf1 support the role of Snf1 activity. Finally, we show that Snf1 is negatively regulated by the rapamycin-sensitive TOR kinase which plays essential roles in signaling nitrogen and amino acid availability. This and other evidence implicate Snf1 in the integration of signals regarding nitrogen and carbon stress. TOR and Snf1/AMPK are highly conserved in evolution, and their novel functional interaction in yeast suggests similar mechanisms in other eukaryotes. 相似文献
109.
110.
Islam MR Jimenez T Pelham C Rodova M Puri S Magenheimer BS Maser RL Widmann C Calvet JP 《The Journal of biological chemistry》2010,285(50):38818-38831