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21.
Apoptosis is essential for the precise regulation of cellular homeostasis and development. The role in vivo of Apaf1, a mammalian homolog of C. elegans CED-4, was investigated in gene-targeted Apaf1-/- mice. Apaf1-deficient mice exhibited reduced apoptosis in the brain and striking craniofacial abnormalities with hyperproliferation of neuronal cells. Apaf1-deficient cells were resistant to a variety of apoptotic stimuli, and the processing of Caspases 2, 3, and 8 was impaired. However, both Apaf1-/- thymocytes and activated T lymphocytes were sensitive to Fas-induced killing, showing that Fas-mediated apoptosis in these cells is independent of Apaf1. These data indicate that Apaf1 plays a central role in the common events of mitochondria-dependent apoptosis in most death pathways and that this role is critical for normal development.  相似文献   
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Ion-implanted GaAs samples have been annealed using a Q-switched ruby laser. Both Si3N4 capped and uncapped samples decomposed and gallium precipitates were formed at the surface. The gallium could be removed by dissolution in HCl to leave high-quality GaAs.  相似文献   
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In the present investigation, three separate projects are described. First, P+ implanted Si is laser and furnace annealed, and the resulting structures as observed by TEM are compared. Second, similar studies are made of Zn+ implanted GaAs, the laser annealing being performed either with or without a surface encapsulating layer. Third, As+ implanted Si is laser annealed, and the uniformity of the annealing process as determined by SEM EBIC studies is assessed. The results have shown that different damage structures can be produced by laser annealing compared to furnace annealing, and by different laser energy densities. For the laser annealed specimens, the TEM observations provided evidence for the formation of a molten surface layer. The results demonstrated for GaAs that encapsulation was still required for laser annealing, and for Si that laser annealing can give a varying p-n junction depth within individual slices. The latter is explained by a molten surface layer extending to different depths during the annealing process, this being attributed to spatial variations in laser intensity across the area illuminated.  相似文献   
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A general theory for the identification of criteria within which an enzymic reaction can exhibit multiplicity (i.e. multiple steady states) is reviewed. Application of the theory to four types of kinetic models encountered in biochemical reactions is illustrated and figures are presented to delineate the region of multiplicity. The stability of the steady states is analysed for small perturbation about the steady state.  相似文献   
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通过采用GT-Styrene苯乙烯回收技术对传统的裂解汽油处理工艺进行改进,汽油的产品性能可以得到有效的改善,并回收有价值的苯乙烯产品和得到高质量的混合二甲苯产品。  相似文献   
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NMDA receptors play important roles in learning and memory and in sculpting neural connections during development. After the period of peak cortical plasticity, NMDA receptor-mediated EPSCs (NMDAR EPSCs) decrease in duration. A likely mechanism for this change in NMDA receptor properties is the molecular alteration of NMDA receptor structure by regulation of NMDA receptor subunit gene expression. The four modulatory NMDAR2A-D (NR2A-D) NMDA receptor subunits are known to alter NMDA receptor properties, and the expression of these subunits is regulated developmentally. It is unclear, however, how the four NR2 subunits are expressed in individual neurons and which NR2 subunits are important to the regulation of NMDA receptor properties during development in vivo. Analysis of NR2 subunit gene expression in single characterized neurons of postnatal neocortex revealed that cells expressing NR2A subunit mRNA had faster NMDAR EPSCs than cells not expressing this subunit, regardless of postnatal age. Expression of NR2A subunit mRNA in cortical neurons at even low levels seemed sufficient to alter the NMDA receptor time course. The proportion of cells expressing NR2A and displaying fast NMDAR EPSCs increased developmentally, thus providing a molecular basis for the developmental change in mean NMDAR EPSC duration.  相似文献   
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PURPOSE: Malignant brain tumors represent a serious therapeutic challenge, and survival often is low. We investigated the delivery of doxorubicin (DXR) to rat brain tumors in situ via liposomes, to test the hypothesis that intact liposomes undergo deposition in intracranial tumor through a compromised blood-tumor vasculature. Both therapeutic effect and intra-tumor drug carrier distribution were evaluated to identify variables in carrier-mediated delivery having impact on therapy. METHODS: The rat 9L gliosarcoma tumor was implanted orthotopically in Fischer 344 rats in the caudate-putamen region. The tumor-bearing rats were treated with DXR, either free or encapsulated in long-circulating, sterically-stabilized liposomes. Anti-tumor efficacy was assessed by survival time. In parallel, liposomes labeled with a fluorescent phospholipid analog were injected into tumor-bearing rats. At predetermined intervals, the brains were perfused with fixative, sectioned, and imaged with laser scanning confocal microscope (LSCM) to investigate the integrity of the tumor vascular bed and the intratumor deposition of liposomes. RESULTS: Free DXR given in 3 weekly iv injections was ineffective in increasing the life span of tumor-bearing rats at cumulative doses < or = 17 mg/kg, and at the highest dose (17 mg/kg) decreased survival slightly, compared to saline-treated controls. In contrast, DXR encapsulated in long-circulating liposomes mediated significant increases in life span at 17 mg/kg. Rats showed a 29% percent increase in median survival, respectively, compared to saline-control animals. The delay of treatment after tumor implantation was a major determinant of therapeutic effect. Fluorescent liposomes were deposited preferentially in tumor rather than normal brain, and were distributed non-uniformly, in close proximity to tumor blood vessels. CONCLUSIONS: Liposomes can be used to enhance delivery of drugs to brain tumors and increase therapeutic effect. The therapeutic effect may arise from release of drug from liposomes extravasated in discrete regions of the tumor vasculature and the extravascular space.  相似文献   
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