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Previous studies have indicated that milrinone, a specific type III phosphodiesterase inhibitor, may be able to induce chloride secretion in cystic fibrosis (CF) tissues. We have now assessed the effect of this agent in vivo on the nasal epithelium of CF mutant mice and also in the nose and lungs of human subjects with CF. Wild-type mice showed a small hyperpolarization of the nasal potential difference (PD) in response to milrinone (100 microM, 1.6 +/- 0.6 mV, n = 8, P < 0.05). In contrast, CF mice carrying either the most common human mutation of the gene for the CF transmembrane regulator (CFTR), DeltaF508 (protein mislocalized), or the G551D mutation (protein normally localized) failed to demonstrate this response. Milrinone perfused alone had no significant effect on the baseline nasal PD of human subjects without CF (14.7 +/- 4.0 mV preperfusion; 15.3 +/- 4.6 mV postperfusion), but significantly (P < 0.05) augmented the hyperpolarization induced by a subsequently perfused low-chloride solution (with milrinone, 36.8 +/- 3.0 mV, n = 6; without milrinone, 18.1 +/- 2.2 mV, n = 19). In contrast, in human subjects with CF (n = 6), milrinone alone significantly (P < 0. 05) altered the nasal baseline PD (52.2 +/- 3.3 mV preperfusion; 57. 4 +/- 4.2 mV, postperfusion) but not the subsequent responses to the low-chloride solution (with milrinone, 1.1 +/- 2.2 mV, n = 4; without milrinone, 0.6 +/- 0.5 mV, n = 28) or to isoproterenol (100 microM). In a separate study in subjects (n = 6) with the DeltaF508 mutation, nasal coadministration of milrinone with isoproterenol produced no effect in the presence of amiloride and a low-chloride solution (-0.8 +/- 0.5 mV). This was also the case in the nasal epithelium of CF subjects (n = 4) carrying at least one G551D allele (-0.3 +/- 0.8 mV). Similarly, milrinone did not hyperpolarize the PD of either the tracheal (n = 6) or segmental (n = 6) airways of CF subjects (DeltaF508) when applied topically in vivo in the presence of amiloride, isoproterenol, or adenosine triphosphate (all 100 microM) in a low-chloride solution. These data do not support the use of milrinone to induce chloride secretion in CF airways in vivo. 相似文献
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The introduction of cyclosporin A has led to improved survival of allografts in humans. However, the use of cyclosporin A is associated with an increased prevalence of hypertension in kidney transplant recipients. Renal vasoconstriction and enhancement of tubular reabsorption contribute to this hypertensive effect. Concomitant treatment with calcium channel blockers blocks or ameliorates most of these adverse effects. This paper reviews the short-term effects of the calcium channel blocker amlodipine on plasma levels of cyclosporin A and its interaction with blood pressure and kidney function. 相似文献
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The technique of group psychotherapy has recently been introduced to the practice in self-assertiveness training group. This study aims to assess various group factors that are hypothesized to be effective in the group process in a self-assertive group. Subjects of the study were participants in a 13-member self-assertiveness training group, with 4 female nurses and 8 male employees and 1 male student. The average age of this group was 35.2 years. Assessment of the group was based on Yalom's concept of twelve therapeutic factors in the group process. The results showed that 'identification', 'The existential factor' and 'interpersonal learning-input' were the three most important factors demonstrated during the group process. There were no significant age and gender differences in the above 'identification' and 'existential' factors. However, different beneficial factors were found for each group: for subjects aged 40 and above and males, it was 'interpersonal learning-output'; while in those with aged under 40 and females, 'universality' was more important than 'interpersonal learning-input'. Comparison of therapeutic factors among different groups was attempted. The above results were found different from patient groups, or the groups of university students. The discrepancy is due to different composition and tasks of each group. 相似文献
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J Bandorowicz-Piku?a A Wrzosek S Piku?a YC Awasthi 《Canadian Metallurgical Quarterly》1997,248(1):238-244
Annexin VI is a 68-kDa calcium-, phospholipid-, and cytoskeletal-element-binding protein, which has been implicated in various processes, including calcium release and sequestration in calcifying cartilage, in a receptor-mediated endocytosis in human fibroblasts, and in secretion from chromaffin granules. In these processes it was found that, in addition to Ca2+ and annexin, the presence of ATP is also a prerequisite. In the present report we show that annexin VI binds ATP and the binding of nucleotide to protein is accompanied by quenching of an intrinsic fluorescence of annexin VI, which was found to be specific for 2'-(or 3')-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate, GTP and ATP, and dependent on the annexin conformation. The nucleotide-binding site within an annexin VI molecule is likely to be close to the tryptophan-containing domain of annexin VI. We propose that ATP plays the role of a physiological ligand for annexin VI, and its binding to annexin VI may represent an alternative cellular mechanism for the regulation of annexin-membrane interactions coupled to overall energy transitions in the cell. 相似文献
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