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GL Burke DE Bild JE Hilner AR Folsom LE Wagenknecht S Sidney 《Canadian Metallurgical Quarterly》1996,1(4):327-335
Copper/zinc (Cu/ZnSOD) and manganese (MnSOD) superoxide dismutases which catalyze the dismutation of toxic superoxide anion, O(2-)-, to O2 and H2O2, play a major role in protecting cells from toxicity of oxidative stress. However, cells overexpressing either form of the enzyme show signs of toxicity, suggesting that too much SOD may be injurious to the cell. To elucidate the possible mechanism of this cytotoxicity, the effect of SOD on DNA and RNA strand scission was studied. High purity preparations of Cu/ZnSOD and MnSOD were tested in an in vitro assay in which DNA cleavage was measured by conversion of phage phi X174 supercoiled double-stranded DNA to open circular and linear forms. Both types of SOD were able to induce DNA strand scission generating single- and double-strand breaks in a process that required oxygen and the presence of fully active enzyme. The DNA strand scission could be prevented by specific anti-SOD antibodies added directly or used for immunodepletion of SOD. Requirement for oxygen and the effect of Fe(II) and Fe(III) ions suggest that cleavage of DNA may be in part mediated by hydroxyl radicals formed in Fenton-type reactions where enzyme-bound transition metals serve as a catalyst by first being reduced by superoxide and then oxidized by H2O2. Another mechanism was probably operative in this system, since in the presence of magnesium DNA cleavage by SOD was oxygen independent and not affected by sodium cyanide. It is postulated that SOD, by having a similar structure to the active center of zinc-containing nucleases, is capable of exhibiting non-specific nuclease activity causing hydrolysis of the phosphodiester bonds of DNA and RNA. Both types of SOD were shown to effectively cleave RNA. These findings may help explain the origin of pathology of certain hereditary diseases genetically linked to Cu/ZnSOD gene. 相似文献
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After a brief presentation of the development of free walking interpreted as learning dynamical equilibrium, the problem of sensory integration in the process of walking development is discussed. A critical review of the role of vision in the development of posturo-locomotor task is presented, along with recent test results on the development of the vestibular system. A final section presents the development of head stabilization and coordination as a necessary means to assist sensory integration. It is suggested that if sensory information is necessary to enhance posturo-locomotor skills, a good mastery of walking is in turn necessary to increase the efficiency of sensory integration. 相似文献
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GL Kay GW Sun A Aoki CA Prejean 《Canadian Metallurgical Quarterly》1995,60(6):1640-50; discussion 1651
BACKGROUND: Preoperative ejection fraction (EF) has been shown to adversely affect postoperative hospital mortality and morbidity for patients undergoing isolated coronary artery bypass grafting. METHODS: To investigate influence of EF on isolated coronary artery bypass grafting outcomes (overall hospital mortality, hospital cardiac mortality, hospital morbidity, and hospital costs), data were reviewed from 1,354 consecutive patients who underwent isolated coronary artery bypass grafting between January 1, 1990, and April 30, 1992, at a single nonprofit hospital. Overall hospital mortality was 4.06% (cardiac, 2.36%). Hospital morbidity was 14.25% (including mortality). Hospital costs (not charges) averaged $16,673 per patient. To explore the impact of preoperative EF, EF was stratified into regular intervals. Each interval was then compared with regard to hospital mortality, morbidity, and average costs. A new statistical tool, discharge analysis, was developed to analyze the cost data. This was necessary because previous efforts at cost analysis have used tools inappropriate for real world cost data. RESULTS: The statistical analysis showed that patients with EF of 0.40 or greater had the best outcomes (lowest mortality, morbidity, and cost). Once the EF is 0.40 or greater the EF does not carry further predictive value. At EF less than 0.40, patients with EF less than 0.30 have a poorer outcome than patients with EF of 0.30 to 0.39. CONCLUSIONS: (1) Ejection fraction is a valid predictor of mortality, morbidity and resource utilization based on statistical analysis. (2) Patients can be broadly grouped as having EF greater than 0.40, less than 0.30, or from 0.30 to 0.39 with regard to clinical and cost outcomes. (3) Postoperative length of stay is not predicted by risk-adjusted EF. (4) A new tool, discharge analysis, is presented to facilitate cost analysis. 相似文献
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GL Solomon 《Canadian Metallurgical Quarterly》1994,102(8):632-635
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G Schuhmachers K Ariizumi T Kitajima D Edelbaum S Xu RK Shadduck GL Gilmore RS Taylor PR Bergstresser A Takashima 《Canadian Metallurgical Quarterly》1996,106(5):1023-1029
We have established long-term dendritic cell lines from the epidermis of newborn mice. These cell lines (XS series) proliferate maximally in response to granulocyte/macrophage-colony stimulating factor, as well as to CSF-1, which is produced by skin-derived NS fibroblast lines and by keratinocytes (albeit in smaller amounts). The purpose of this study was to examine the impact of UVB radiation on CSF-1-mediated interaction of dendritic cells with fibroblasts and keratinocytes. Exposure of NS cells to UVB radiation (unfiltered FS20 sunlamp) decreased CSF-1 production at mRNA and protein levels. Both changes occurred in a dose-dependent fashion, with 50 J/m2 causing a significant reduction. UVB radiation also downregulated CSF-1 mRNA expression by Pam 212 keratinocytes. UVB exposure of XS cells diminished the surface expression of CSF-1 receptors, with 50 J/m2 causing a significant reduction. Thus, UVB radiation interrupts CSF-1-mediated cell-cell interaction by a dual mechanism: downregulating CSF-1 production and abrogating CSF-1 receptor expression. Importantly, granulocyte/macrophage-colony stimulating factor receptor expression by XS cells was also inhibited by UVB radiation, once again, with 50 J/m2 producing significant inhibition. We propose that the resulting CSF-1 deficiency in epidermal microenvironment and unresponsiveness by dendritic cells to relevant growth factors may contribute to UVB-mediated loss of resident epidermal dendritic cells (i.e., Langerhans cells) in skin. 相似文献