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61.
Transient accumulation, phosphorylation and changes in the oligomerization of Hsp27 during retinoic acid-induced differentiation of HL-60 cells: possible role in the control of cellular growth and differentiation 总被引:2,自引:0,他引:2 下载免费PDF全文
Expression of the mammalian small stress protein Hsp27 has been increasingly linked to cell growth regulation and differentiation. Hsp27 is a phosphoprotein which forms oligomers with native sizes ranging between 100 and 800 kDa. We have examined the fate of Hsp27 transiently expressed during the retinoic acid (tRA)-induced granulocytic differentiation of human leukemic HL-60 cells. We show that tRA, in addition to its effects on Hsp27 accumulation and phosphorylation, transiently increased the oligomerization state of this protein. While Hsp27 phosphorylation by tRA is an early phenomenon that takes place before cellular growth is altered, the redistribution of Hsp27 oligomers occurred later and concomitantly with the maximal accumulation of this protein. Hence, complex regulations of Hsp27 are induced by tRA which suggest that this protein plays a role in the pathway through which retinoids exert their effects. To approach Hsp27 function during HL-60 cell differentiation, experiments aimed at reducing the cellular content of this protein were performed by transiently inhibiting Hsp27 mRNA translation by a specific anti-sense oligonucleotide. This process, which decreased the basal level of Hsp27 by about 40%, did not interfere with the growth of undifferentiated HL-60 cells. In contrast, a decreased level of Hsp27 diminished the differentiation-mediated down-regulation of cell growth and altered some morphological changes induced by this retinoid. These results suggest that Hsp27 is a mediator of granulocytic differentiation. 相似文献
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Breast cancer is the most frequent malignancy in women and drug resistance is the major obstacle for its successful chemotherapy. In the present study, we analyzed the involvement of an oncofetal gene, sal-like 4 (SALL4), in the tumor proliferation and drug resistance of human breast cancer. Our study showed that SALL4 was up-regulated in the drug resistant breast cancer cell line, MCF-7/ADR, compared to the other five cell lines. We established the lentiviral system expressing short hairpin RNA to knockdown SALL4 in MCF-7/ADR cells. Down-regulation of SALL4 inhibited the proliferation of MCF-7/ADR cells and induced the G1 phase arrest in cell cycle, accompanied by an obvious reduction of the expression of cyclinD1 and CDK4. Besides, down-regulating SALL4 can re-sensitize MCF-7/ADR to doxorubicin hydrochloride (ADMh) and had potent synergy with ADMh in MCF-7/ADR cells. Depletion of SALL4 led to a decrease in IC50 for ADMh and an inhibitory effect on the ability to form colonies in MCF-7/ADR cells. With SALL4 knockdown, ADMh accumulation rate of MCF-7/ADR cells was increased, while the expression of BCRP and c-myc was significantly decreased. Furthermore, silencing SALL4 also suppressed the growth of the xenograft tumors and reversed their resistance to ADMh in vivo. SALL4 knockdown inhibits the growth of the drug resistant breast cancer due to cell cycle arrest and reverses tumor chemo-resistance through down-regulating the membrane transporter, BCPR. Thus, SALL4 has potential as a novel target for the treatment of breast cancer. 相似文献
64.
Acetylation and methylation patterns of core histones are modified after heat or arsenite treatment of Drosophila tissue culture cells 总被引:2,自引:0,他引:2 下载免费PDF全文
A P Arrigo 《Nucleic acids research》1983,11(5):1389-1404
Exposure of Drosophilamelanogaster tissue culture cells to 37 degrees C (heat shock) or to arsenite induces a severe deacetylation of core histones and blocks the methylation of histone H(3) and H(4). Heat shock induces the methylation of histone H(2b). These results are discussed in view of chromatin structure and function.Images 相似文献
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Cellular localization of HSP23 during Drosophila development and following subsequent heat shock 总被引:6,自引:0,他引:6
A P Arrigo 《Developmental biology》1987,122(1):39-48
The low-molecular-weight heat-shock protein HSP23 is synthesized in the absence of heat shock during Drosophila development. Here, I present a quantitative analysis of this phenomenon and describe the cellular localization of this protein during normal development and after a subsequent heat shock. HSP23 is first detected in the late third instar larvae and continues to accumulate reaching a maximum level in late pupae. In a 1-week-old adult, HSP23 can no longer be detected. Following lysis of whole pupae, HSP23 is found in the soluble lysate fraction in a form which sediments between 10 and 20 S. Exposure of larvae, pupae, and the adult fly to heat stress (37 degrees C) results in an increased amount of HSP23 which, however, is recovered in an insoluble particulate form following insect lysis. During recovery from heat shock, HSP23 is again found in the soluble 10- to 20-S lysate fraction. In pupae which are exposed to a severe heat stress (41 degrees C) HSP23 remains in the pellet fraction after the heat stress and no pupae are able to emerge as adult flies. However, when pupae are first exposed to a mild heat-shock treatment prior to the 41 degrees C stress, the thermotolerance process is induced and HSP23 is again rapidly found in the soluble lysate fraction during the recovery from heat shock. These observations suggest a possible correlation between the survival of pupae after heat shock and the recovery of HSP23 in the soluble lysate fraction as 10- to 20-S structures after the heat shock. 相似文献
67.
A cellular protein phosphorylated by the avian sarcoma virus transforming gene product is associated with ribonucleoprotein particles 总被引:4,自引:3,他引:1 下载免费PDF全文
In chick embryo fibroblasts transformed by Rous sarcoma virus (RSV) the tyrosine phosphorylation of a cellular protein of 34,000 daltons mol. wt. (34 kd) is greatly enhanced; this was shown to be catalyzed by the phosphotransferase activity of RSV transforming protein pp60src. We report here that in cytoplasmic extracts of both normal and transformed cells, in the presence of magnesium ions, the majority of the 34-kd protein is associated with large structures and that a fraction of 34 kd appears to be associated with ribonucleoprotein particles (RNPs). In addition, upon u.v. light cross-linking of RNA to protein in normal or transformed cells, an anti-34 kd serum immunoprecipitates RNA fragments of apparent low sequence complexity as detected by T1 fingerprint analysis. Our results indicate that the 34-kd protein may play a role in the cell at the level of RNPs. 相似文献
68.
Mapping U2 snRNP--pre-mRNA interactions using biotinylated oligonucleotides made of 2''-OMe RNA. 总被引:21,自引:3,他引:18 下载免费PDF全文
Biotinylated 2'-OMe RNA oligonucleotides complementary to two separate regions of human U2 snRNA have been used as affinity probes to study U2 snRNP--pre-mRNA interactions. Both oligonucleotides bind specifically and allow highly selective removal of U2 snRNP from HeLa cell nuclear extracts. Pre-mRNA substrates can also be specifically affinity selected through oligonucleotides binding to U2 snRNP particles in splicing complexes. Stable binding of U2 snRNP to pre-mRNA is blocked by the pre-binding of an oligonucleotide to the branch site complementary region of U2 snRNA, but not by an oligonucleotide binding to the 5' terminus of U2. Both oligonucleotides affinity select the intron product, but not the intron intermediate, when added after spliceosome assembly has taken place. The effect of 2'-OMe RNA oligonucleotides on splicing complex formation has been used to demonstrate that complexes containing U2 snRNP and unspliced pre-mRNA are precursors to functional spliceosomes. 相似文献
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