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1.
Autoregulation of tubulin expression is achieved through specific degradation of polysomal tubulin mRNAs 总被引:34,自引:0,他引:34
We have utilized protein synthesis inhibitors to investigate the autoregulatory mechanism that uses the concentration of unpolymerized tubulin subunits to specify tubulin mRNA content in animal cells. Puromycin and pactamycin, both of which remove RNAs from polysomes, completely unlink tubulin RNA content from the level of free subunits, whereas pretreatment of cells with cycloheximide, which traps mRNAs onto stalled polyribosomes, enhances the specific degradation of tubulin RNAs in response to increases in the subunit content. Moreover, in the absence of protein synthesis inhibitors, the tubulin RNAs that are lost from cells with elevated free tubulin subunit levels are those that are associated with polyribosomes. Further, beta-tubulin mRNAs encoding a truncated translation product of only 26 amino acids (and that cannot be polyribosomal) are not substrates for autoregulation. We conclude that autoregulation of tubulin synthesis is achieved by specifically altering the stability of tubulin RNAs that are bound to polyribosomes. 相似文献
2.
Role of c-myc and other genes in interleukin 2 regulated CT6 T lymphocytes and their malignant variants 总被引:6,自引:0,他引:6
J L Cleveland U R Rapp W L Farrar 《Journal of immunology (Baltimore, Md. : 1950)》1987,138(10):3495-3504
The cloned murine cytotoxic T cell line CT6 solely requires interleukin 2 (IL 2) for viability and cell cycle progression. Treatment of G arrested cultures of CT6 cells with recombinant IL 2 induces the rapid sequential expression of the nuclear proto-oncogenes c-fos, c-myc, and c-myb but does not affect the expression of several cytosolic or membrane-associated proto-oncogenes. A comparison of early genes induced by growth factor treatment of quiescent NIH/3T3 fibroblasts and CT6 cells demonstrated that only c-fos and c-myc induction is shared in the two different lineages. Factor-independent lines derived from CT6 cells show no mitogenic response to IL 2, yet binding of IL 2 with its receptor in the cells was capable of inducing the expression of c-fos and c-myc. In factor-independent cell lines, c-myc was uniformly expressed at high constitutive levels, suggesting that c-myc abrogates growth factor requirements of these cells. The levels of c-myc expression in the factor-independent lines was not due to an autocrine production of IL 2 but may be a consequence of constitutively activated IL 2 receptors. 相似文献
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Multiple determinants of eukaryotic mRNA stability 总被引:37,自引:0,他引:37
Regulated changes in mRNA stability play an important role in modulating the level of expression of many eukaryotic genes. In several systems, specific sequence determinants that dictate mRNA instability have been identified. Thus, the presence of instability determinants, and not the absence of sequences that dictate stability, appears to be required for regulated mRNA degradation. These instability determinants presumably interact with specific nucleases or other trans-acting factors that regulate the accessibility of the domain to nucleases. Although each RNA destabilization pathway has unique features, in many cases RNA degradation requires ongoing protein synthesis. In some of the systems discussed, the mRNAs are degraded co-translationally, perhaps by a ribosome-associated ribonuclease. For other messages, the mechanistic reasons for the dependence of mRNA degradation on ongoing protein synthesis are still unknown. 相似文献
10.
Perng-Kuang Chang Jeffrey W. Cary Jiujiang Yu Deepak Bhatnagar Thomas E. Cleveland 《Molecular genetics and genomics : MGG》1995,248(3):270-277
Aflatoxins comprise a group of polyketide-derived carcinogenic mycotoxins produced byAspergillus parasiticus andAspergillus flavus. By transformation with a disruption construct, pXX, we disrupted the aflatoxin pathway inA. parasiticus SRRC 2043, resulting in the inability of this strain to produce aflatoxin intermediates as well as a major yellow pigment in the transformants. The disruption was attributed to a single-crossover, homologous integration event between pXX and the recipientA. parasiticus genome at a specific locus, designatedpksA. Sequence analysis suggest thatpksA is a homolog of theAspergillus nidulans wA gene, a polyketide synthase gene involved in conidial wall pigment biosynthesis. The conservedβ-ketoacyl synthase, acyltransferase and acyl carrier-protein domains were present in the deduced amino acid sequence of thepksA product. Noβ-ketoacyl reductase and enoyl reductase domains were found, suggesting thatpksA does not encode catalytic activities for processingβ-carbon similar to those required for long chain fatty acid synthesis. ThepksA gene is located in the aflatoxin pathway gene cluster and is linked to thenor-1 gene, an aflatoxin pathway gene required for converting norsolorinic acid to averantin. These two genes are divergently transcribed from a 1.5 kb intergenic region. We propose thatpksA is a polyketide synthase gene required for the early steps of aflatoxin biosynthesis. 相似文献