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排序方式: 共有96条查询结果,搜索用时 46 毫秒
71.
Manca Tekav
i
Pompe Nika Vrabi
Marija Volk Andrej Megli
Martina Jarc-Vidmar Borut Peterlin Marko Hawlina Ana Fakin 《Current issues in molecular biology》2021,43(2):941
Achromatopsia has been proposed to be a morphologically predominately stable retinopathy with rare reports of progression of structural changes in the macula. A five-grade system of optical coherence tomography (OCT) features has been used for the classification of structural macular changes. However, their association with age remains questionable. We characterized the Slovenian cohort of 12 patients with pathogenic variants in CNGA3 or CNGB3 who had been followed up with OCT for up to 9 years. Based on observed structural changes in association with age, the following four-stage classification of retinal morphological changes was proposed: (I) preserved inner segment ellipsoid band (Ise), (II) disrupted ISe, (III) ISe loss and (IV) ISe and RPE loss. Data from six previously published studies reporting OCT morphology in CNGA3 and CNGB3 patients were additionally collected, forming the largest CNGA3/CNGB3 cohort to date, comprising 126 patients aged 1–71 years. Multiple regression analysis showed a significant correlation of OCT stage with age (p < 0.001) and no correlation with gene (p > 0.05). The median ages of patients with stages I–IV were 12 years, 23 years, 27 years and 48 years, respectively, and no patient older than 50 years had continuous ISe. Our findings suggest that achromatopsia presents with slowly but steadily progressive structural changes of the macular outer retinal layers. However, whether morphological changes in time follow the proposed four-stage linear pattern needs to be confirmed in a long-term study. 相似文献
72.
73.
A peptidomics strategy to elucidate the proteolytic pathways that inactivate peptide hormones 总被引:1,自引:0,他引:1
Tinoco AD Kim YG Tagore DM Wiwczar J Lane WS Danial NN Saghatelian A 《Biochemistry》2011,50(12):2213-2222
Proteolysis plays a key role in regulating the levels and activity of peptide hormones. Characterization of the proteolytic pathways that cleave peptide hormones is of basic interest and can, in some cases, spur the development of novel therapeutics. The lack, however, of an efficient approach to identify endogenous fragments of peptide hormones has hindered the elucidation of these proteolytic pathways. Here, we apply a mass spectrometry (MS) based peptidomics approach to characterize the intestinal fragments of peptide histidine isoleucine (PHI), a hormone that promotes glucose-stimulated insulin secretion (GSIS). Our approach reveals a proteolytic pathway in the intestine that truncates PHI at its C-terminus to produce a PHI fragment that is inactive in a GSIS assay, a result that provides a potential mechanism of PHI regulation in vivo. Differences between these in vivo peptidomics studies and in vitro lysate experiments, which showed N- and C-terminal processing of PHI, underscore the effectiveness of this approach to discover physiologically relevant proteolytic pathways. Moreover, integrating this peptidomics approach with bioassays (i.e., GSIS) provides a general strategy to reveal proteolytic pathways that may regulate the activity of peptide hormones. 相似文献
74.
We report a new method for the preparation of proteins in a form suitable for high-sensitivity N-terminal amino acid sequence analysis. Proteins separated by polyacrylamide gel electrophoresis were electrophoretically transferred onto glass fiber filter paper chemically activated by the introduction of phenyl isothiocyanate functional groups. The proteins became covalently coupled to the matrix during the electrotransfer process. Bands containing transferred proteins were detected by fluorescent staining or autoradiography, cut out from the glass fiber filter, and directly loaded into the cartridge of a gas-phase sequenator. The covalent nature of the interactions between protein and glass fiber support permitted the use of more vigorous solid-phase sequencing protocols and of alternative sequencing reagents. This high-efficiency isolation and covalent coupling method provides the essential first step toward enhanced-sensitivity protein sequence analysis. The method has been successfully applied to the isolation of a wide variety of proteins from SDS-polyacrylamide gels, and was shown to be compatible with both the standard Edman reagent phenyl isothiocyanate and alternative sequencing reagents such as 4-(N,N'-dimethylamino)azobenzene-4'-isothiocyanate (DABITC). 相似文献
75.
Lectin-binding curves are reported for a concanavalin A receptor glycoprotein in lipid bilayers and intact cells. The results are consistent with previous studies of the structurally dissimilar transmembrane glycoprotein, glycophorin. High-affinity lectin binding to model membranes was influenced by the presence of apparently unrelated macromolecules, which we suggest is an example of receptor modulation by local interactions. Furthermore, high-affinity binding to the model membranes displayed characteristics, including positive cooperativity, similar to those seen with intact cells. 相似文献
76.
Direct Interaction of Jak1 and v-Abl Is Required for v-Abl-Induced Activation of STATs and Proliferation 总被引:9,自引:2,他引:7
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77.
Nika V. Ketis Jack Lawler William G. Bendena 《In vitro cellular & developmental biology. Animal》1993,29(10):768-772
Summary The biosynthetic profile of endothelial cells responding to hyperthermia is altered by extracellular matrix components. The
extracellular matrix components influence the quantitative expression of members of the HSP70 family and HSP90. The expression
of several HSP70 mRNA species, which are strictly stress inducible, are modulated by extracellular matrix components. Both
laminin and collagen type IV decrease the amount of HSP70 protein and mRNA expressed by endothelial cells exposed to hyperthermia
relative to control cultures attached to virgin plastic. In contrast, both laminin and collagen type IV increased the amount
of HSP90 mRNA constitutively expressed by endothelial cells at 37° C. When endothelial cells were exposed to elevated temperatures,
these two extracellular matrix proteins decrease the amount of HSP90 mRNA relative to control cultures attached to virgin
plastic. Our observations are consistent with the proposal that the extracellular matrix components regulate gene expression
and cell behavior in regard to thermotolerance. 相似文献
78.
Cell death: critical control points 总被引:146,自引:0,他引:146
Programmed cell death is a distinct genetic and biochemical pathway essential to metazoans. An intact death pathway is required for successful embryonic development and the maintenance of normal tissue homeostasis. Apoptosis has proven to be tightly interwoven with other essential cell pathways. The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics. 相似文献
79.
The v-Abl oncogene activates Jak-Stat signaling during transformation of pre-B cells in mice. Disrupting Jak activation by deleting the Jak binding domain of v-Abl or by expressing a dominant-negative Jak1 decreases v-Abl transformation efficiency. As SOCS-1 is a known potent inhibitor of Jak kinases, the mechanism by which v-Abl bypasses SOCS-1 regulation to constitutively activate Jak kinases was investigated. SOCS-1 is expressed in v-Abl-transformed cells but is unable to inhibit v-Abl-mediated Jak-Stat signaling. In v-Abl transformants, SOCS-1 can inhibit cytokine signals, but it is more efficient at doing so when the cells are treated with STI571, an Abl kinase inhibitor. Downstream effects of v-Abl signaling include phosphorylation of SOCS-1 on nontyrosine residues, disruption of the interaction between SOCS-1 and the Elongin BC complex, and inhibition of SOCS-1-mediated proteasomal targeting of activated Jaks. These findings reveal a mechanism by which Jak-dependent oncogenes may bypass SOCS-1 inhibition. 相似文献
80.
Nika J Yang W Pavitt GD Hinnebusch AG Hannig EM 《The Journal of biological chemistry》2000,275(34):26011-26017
Eukaryotic translation initiation factor 2B (eIF2B) is the heteropentameric guanine nucleotide exchange factor for translation initiation factor 2 (eIF2). Recent studies in the yeast Saccharomyces cerevisiae have served to characterize genetically the exchange factor. However, enzyme kinetic studies of the yeast enzyme have been hindered by the lack of sufficient quantities of protein suitable for biochemical analysis. We have purified yeast eIF2B and characterized its catalytic properties in vitro. Values for K(m) and V(max) were determined to be 12.2 nm and 250.7 fmol/min, respectively, at 0 degrees C. The calculated turnover number (K(cat)) of 43.2 pmol of GDP released per min/pmol of eIF2B at 30 degrees C is approximately 1 order of magnitude lower than values previously reported for the mammalian factor. Reciprocal plots at varying fixed concentrations of the second substrate were linear and intersected to the left of the y axis. This is consistent with a sequential catalytic mechanism and argues against a ping-pong mechanism similar to that proposed for EF-Tu/EF-Ts. In support of this model, our yeast eIF2B preparations bind guanine nucleotides, with an apparent dissociation constant for GTP in the low micromolar range. 相似文献