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101.
Porcine sperm factor supports activation and development of bovine nuclear transfer embryos 总被引:7,自引:0,他引:7
A study was undertaken to determine whether injection of porcine sperm factors (pSF), which trigger oscillations in intracellular calcium concentration ([Ca(2+)](i)) in mammalian oocytes, could be used to activate bovine oocytes during nuclear transfer. To date, only combined treatments that induce a monotonic rise in [Ca(2+)](i) and inhibit either phosphorylation or protein synthesis have been utilized in nuclear transfer. Several doses of pSF were tested. Injection of 5 mg/ml pSF triggered [Ca(2+)](i) oscillations that resembled those associated with fertilization with respect to amplitude and periodicity, and as a result, a high percentage of oocytes underwent activation. Furthermore, this concentration of pSF supported in vitro and in vivo development up to 60-90 days of gestation, comparable to development in control nuclear transfer embryos. Nevertheless, neither activation procedure supported development as well as did fertilization. The effectiveness of pSF as an activating agent in bovine oocytes may have been compromised because pSF was unable to support oscillations past 3-5 h postinjection and a second injection was necessary to extend the [Ca(2+)](i) oscillations. Likewise, a single injection of pSF failed to trigger downregulation of the inositol 1,4,5-trisphosphate receptor 1 subtype, whereas a second injection downregulated the receptor in a manner similar to that seen in fertilized oocytes. These results demonstrate that soluble factor(s) from porcine sperm can support early development in bovine nuclear transfer embryos; however, the efficacy may be limited because of the premature cessation of the induced oscillations. 相似文献
102.
Whiteman P Smallridge RS Knott V Cordle JJ Downing AK Handford PA 《The Journal of biological chemistry》2001,276(20):17156-17162
Human fibrillin-1, an extracellular matrix glycoprotein, has a modular organization that includes 43 calcium-binding epidermal growth factor-like (cbEGF) domains arranged as multiple tandem repeats. A missense mutation that changes a highly conserved glycine to serine (G1127S) has been identified in cbEGF13, which results in a variant of Marfan syndrome, a connective tissue disease. Previous experiments on isolated cbEGF13 and a cbEGF13-14 pair indicated that the G1127S mutation caused defective folding of cbEGF13 but not cbEGF14. We have used limited proteolysis methods and two-dimensional NMR spectroscopy to identify the structural consequences of this mutation in a covalently linked cbEGF12-13 pair and a cbEGF12-14 triple domain construct. Protease digestion studies of the cbEGF12-13 G1127S mutant pair indicated that both cbEGF12 and 13 retained similar calcium binding properties and thus tertiary structure to the normal domain pair, because all identified cleavage sites showed calcium-dependent protection from proteolysis. However, small changes in the conformation of cbEGF13 G1127S, revealed by the presence of a new protease-sensitive site and comparative two-dimensional NOESY data, suggested that the fold of the mutant domain was not identical to the wild-type, but was native-like. Additional cleavage sites identified in cbEGF12-14 G1127S indicated further subtle changes within the mutant domain but not the flanking domains. We have concluded the following in this study. (i) Covalent linkage of cbEGF12 preserves the native-like fold of cbEGF13 G1127S and (ii) conformational effects introduced by G1127S are localized to cbEGF13. This study demonstrates that missense mutations in fibrillin-1 cbEGF domains can cause short range structural effects in addition to long range effects previously observed with a E1073K mutation in cbEGF12. 相似文献
103.
Rösler A Bailey L Jones S Briggs J Cuss S Horsey I Kenrick M Kingsmore S Kent L Pickering J Knott T Shipstone E Scozzafava G 《Nucleosides, nucleotides & nucleic acids》2001,20(4-7):893-894
The analysis of the genetic basis of phenotypic traits is moving towards the complex diseases prevalent in wealthy populations. There is an increasing requirement for the detection of different types of sequence variation, particularly single-nucleotide polymorphisms (SNPs). SNPs occur about once every 100 to 300 bases. High-density SNP maps will help to identify the multiple genes associated with complex diseases such as cancer, diabetes, vascular disease, and some forms of mental illness. 相似文献
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Gudrun A. Brockmann Ersin Karatayli Christina Neuschl Ioannis M. Stylianou Soner Aksu Antje Ludwig Ulla Renne Chris S. Haley Sara Knott 《Mammalian genome》2007,18(11):757-766
An F2 pedigree based on the mouse lines DU6i and DBA/2 with extremely different growth and obesity characteristics was generated
to search for QTLs affecting serum concentrations of triglycerides (TG), total cholesterol (CHOL), HDL cholesterol (HDL-C),
and LDL cholesterol (LDL-C). Compared with many other studies, we searched for spontaneous genetic variants contributing to
high lipid levels under a standard breeding diet. Significant QTLs for CHOL were identified on chromosomes 4 and 6, and a
female-specific locus on chromosome 3. QTLs for HDL-C were detected on chromosome 11 for both sexes, and on chromosome 1 for
females. These QTLs are located in syntenic human regions that have QTLs that have not been previously confirmed in animal
studies. LDL-C QTLs have been mapped for both sexes to chromosome 8 and in males on chromosome 13. Epistatic interactions
that significantly accounted for the phenotypic variance of HDL-C, CHOL, and LDL-C serum concentrations were also detected
with one interaction between chromosomes 8 and 15, accounting for 22% of the observed variance in LDL-C levels. The identified
loci coincide in part with regions controlling growth and obesity. Thus, multiple genes or pleiotropic effects may be assumed.
The identified QTLs for cholesterol and its transport proteins as subcomponents of risk for coronary heart disease will further
improve our understanding of the genetic net controlling plasma lipid concentrations.
Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users. 相似文献
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Trace metal (Zn, Pb, Cu, Cr and Cd) concentrations in the water column and in the liver, muscle and gill tissues of Parachanna obscura and Clarias gariepinus in Agulu Lake, Nigeria, were investigated in June 2014 and compared with WHO and FAO safe limits for water and fish. Hazard index (HI) values were estimated to assess the potential public health risk of consuming contaminated fish. Lead and cadmium exceeded WHO guideline values for drinking water. In most cases, variations in concentration of the metals in organs were liver > muscle > gill. Differences in tissue-specific concentrations between species were not significant, except for zinc in muscles and gills. Cadmium and chromium were not detected in the fish, but lead was above the FAO maximum value for consumption. Hazard index values were below 1, indicating a low risk to public health. However, trace metal contamination in Agulu Lake is increasing. 相似文献
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