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991.
In Saccharomyces cerevisiae, the phosphatidylinositol kinase homologue Tor2 controls the cell-cycle-dependent organisation of the actin cytoskeleton by activating the small GTPase Rho1 via the exchange factor Rom2 [1,2]. Four Rho1 effectors are known, protein kinase C 1 (Pkc1), the formin-family protein Bni1, the glucan synthase Fks and the signalling protein Skn7 [2,3]. Rho1 has been suggested to signal to the actin cytoskeleton via Bni1 and Pkc1; rho1 mutants have never been shown to have defects in actin organisation, however [2,4]. We have further investigated the role of Rho1 in controlling actin organisation and have analysed which of the Rho1 effectors mediates Tor2 signalling to the actin cytoskeleton. We show that some, but not all, rho1 temperature-sensitive (rho1ts) mutants arrest growth with a disorganised actin cytoskeleton. Both the growth defect and the actin organisation defect of the rho1-2ts mutant were suppressed by upregulation of Pkc1 but not by upregulation of Bni1, Fks or Skn7. Overexpression of Pkc1, but not overexpression of Bni1, Fks or Skn7, also rescued a tor2ts mutant, and deletion of BNI1 or SKN7 did not prevent the suppression of the tor2ts mutation by overexpressed Rom2. Furthermore, overexpression of the Pkc1-controlled mitogen-activated protein (MAP) kinase Mpk1 suppressed the actin defect of tor2ts and rho1-2ts mutants. Thus, Tor2 signals to the actin cytoskeleton via Rho1, Pkc1 and the cell integrity MAP kinase cascade. 相似文献
992.
993.
We have detected an anhydride intermediate in the CPA catalyzed proteolytic reaction of Gly-Tyr. It appears that since the zinc-bound water molecule which is believed to attack the scissile amide carbonyl carbon in the hydrolysis reaction is excluded by the N-terminal amino group of Gly-Tyr, the carboxylate of Glu-270 becomes to attack the amide bond to generate the anhydride intermediate. 相似文献
994.
JD Brierley AJ Rathmell MK Gospodarowicz SB Sutcliffe A Munro R Tsang M Pintilie 《Canadian Metallurgical Quarterly》1998,77(8):1300-1310
A comprehensive survey of late effects (physical, social and reproductive) following treatment at a single institution for early stage Hodgkin's disease (HD) was performed. A total of 611 patients with stage I and II HD treated between 1973 and 1984 were reviewed; 460 were alive and were mailed a self-reported questionnaire. A total of 363 (79%) replies were received. Twenty patients died of second malignancy, 14 of heart disease and nine from respiratory disease. There were 37 cases of second malignancy [relative risk (RR) 2.2, absolute excess risk (AR) 35.8]. The 15-year incidence of heart disease was 11% and there were nine myocardial infarction deaths (RR 1.55, AR 5.4). Twenty-eight (8%) respondents stated that their career had been greatly interfered with, 53 (14.5%) perceived financial loss. Sexual activity was disrupted in 25.8%. In total, 56 men had fathered 112 pregnancies. Of 171 women, 40.3% became pregnant, resulting in 92 live births. A total of 43 men and 16 women had sought medical advice with regard to infertility. 相似文献
995.
996.
997.
To assess the typical drinking situations of high anxiety sensitive individuals, relative to low anxiety sensitive individuals, a large sample of university student drinkers (N = 396) completed the 42-item version of the Inventory of Drinking Situations (IDS-42) and the Anxiety Sensitivity Index (ASI). As hypothesized, ASI scores were significantly positively correlated with drinking frequency on the higher order IDS-42 factor of negatively reinforcing drinking situations and not significantly correlated with drinking frequency on the higher order factor of positively reinforcing drinking situations. Also, ASI scores were significantly positively correlated with drinking frequency on the lower order drinking situations factors of Conflict with Others, Unpleasant Emotions, and Physical Discomfort. ASI scores were also unexpectedly significantly correlated with more frequent drinking on the higher order factor of temptation drinking situations and with more frequent drinking on the lower order drinking situations factor of Testing Personal Control. These results have important implications for designing early prevention and intervention programs for high anxiety sensitive university student drinkers by helping them to develop alternatives to drinking in those situations (e.g., negatively reinforcing drinking situations) which place them at greatest risk for alcohol misuse. 相似文献
998.
H Gong R Wong RJ Sarma WS Linn ED Sullivan DA Shamoo KR Anderson SB Prasad 《Canadian Metallurgical Quarterly》1998,158(2):538-546
We hypothesized that ozone (O3) exposure acutely affects cardiovascular hemodynamics in humans and, in particular, in subjects with essential hypertension. We studied 10 nonmedicated hypertensive and six healthy male adults. Each subject, after catheterization of the right heart and a radial artery, was exposed in an environmentally controlled chamber to filtered air (FA) on one day and to 0.3 ppm O3 on the following day for 3 h with intermittent exercise. Relative to FA exposure, O3 exposure induced no statistically significant changes in cardiac index, ventricular performance, pulmonary artery pressure, pulmonary and systemic vascular resistances, ECG, serum cardiac enzymes, plasma catecholamines and atrial natriuretic factor, and SaO2. The overall results did not indicate major acute cardiovascular effects of O3 in either the hypertensive or the control subjects. However, mean preexposure to postexposure changes were significantly (p < 0.02) larger with O3 than with FA for rate-pressure product (1,353 beats/min/mm Hg) and for heart rate (8 beats/min); these responses were not significantly different between the hypertensive and the control subjects. Significant O3 effects were also observed for mean FEV1 (-6%), and AaPO2 (> 10 mm Hg increase), which were not significantly different between the two groups. These results suggest that O3 exposure can increase myocardial work and impair pulmonary gas exchange to a degree that might be clinically important in persons with significant preexisting cardiovascular impairment, with or without concomitant lung disease. 相似文献
999.
The nongenomic action of progesterone (P) on capacitated sperm in mediating acrosomal exocytosis operates through transmembrane signal transduction involving increased intracellular calcium ions and modulation of protein kinases and phospholipid metabolism through a second messenger pathway. Conflicting views exist regarding the nature of the nongenomic receptor of P. It is thought to be a cell-surface receptor having the properties of a calcium channel, chloride channel, bicarbonate/chloride exchanger, and gamma aminobutyric acid type A (GABA(A)). In this study, we tried to understand the role of bicarbonate and/or P in inducing membrane perturbations in capacitated and acrosome-reacting spermatozoa. We also attempted to characterize the membrane responses in P-stimulated and bicuculline-poisoned sperm. The presence of a high level of bicarbonate in the medium favored high rotational mobility of lipids and proteins in capacitated sperm. However, the capacitated sperm exhibited low lipid ordering and unaltered protein ordering in response to the high bicarbonate concentration. P and bicuculline appeared to bind to the same or similar binding sites, probably a GABA(A) receptor, eliciting similar motional perturbations in sperm membranes. It appears that both P and bicuculline can induce receptor aggregation and lipid ordering in sperm membranes, which alter the capability of sperm to bind zona pellucida, and that the P action on sperm takes effect through a bicarbonate-dependent signal transduction mechanism. 相似文献
1000.
The distribution and clinicopathologic features of pancreatic fibrosis were studied histopathologically in 137 autopsy cases of chronic alcohol abuse. Fibrosis was observed in 90 of the cases and was classified as perilobular sclerosis (PS) and intralobular sclerosis (IS). Fibrosis of the PS type was irregular and sometimes patchy and extended into the intralobular area in advanced cases. In some advanced cases, complete replacement of the pancreatic tissue by extensive fibrosis was seen. Fibrosis of the IS type was uniformly distributed. The tissues in some cases showed prominently periacinar fibrosis. In these cases, the pancreatic parenchyma had not been completely replaced by extensive fibrosis. Clinicopathologic comparisons revealed the following results: accompanying liver cirrhosis was greater in the IS than in the PS of fibrosis. However, a higher frequency of protein plugs, pancreatic stones, extensive fibrosis replacement, peripancreatic fibrosis, splenic vein involvement, choledochus involvement, pseudocyst, and ductal hyperplasia was found in the PS type compared to the IS type. In conclusion, the findings on the perilobular and intralobular distribution of fibrosis and differences in various components or accompanying diseases in pancreatic fibrosis suggest that this entity shows two distinct pathologic patterns with differing mechanisms. 相似文献