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991.
OBJECTIVE: To assess the hypoglycemic effect and the insulin-releasing effect of the main glyburide (glibenclamide) metabolites 4-trans-hydroxy-glibenclamide (M1) and 3-cis-hydroxy-glibenclamide (M2) in humans. RESEARCH DESIGN AND METHODS: Eight healthy subjects participated in a placebo-controlled, randomized, single-blind crossover study with five single-dose tests, 3 months apart: 3.5 mg glibenclamide (Gb) orally, 3.5 mg Gb intravenously, 3.5 mg M1 intravenously, 3.5 mg M2 intravenously, and placebo intravenously, each in the fasting state. Standardized meals were given 0.5 and 5.5 h after each medication. Blood glucose levels were measured by a glucose oxidase method, and serum insulin concentrations were analyzed by a specific immunoassay. RESULTS: Blood glucose levels during the first 5 h were significantly lowered not only by Gb but also by M1 and M2. The mean +/- SE blood glucose reductions (versus placebo) expressed as percent of area under the curve (AUC) (0-5 h) were 18.2 +/- 3.3% for M1, 12.5 +/- 2.3% for M2, 19.9 +/- 2.1% for intravenous Gb, and 23.8 +/- 1.2% for Gb orally. Serum insulin levels were significantly increased by Gb as well as by M1 and M2. and M2. CONCLUSIONS: The two main metabolites of glyburide (glibenclamide) have a hypoglycemic effect in humans, which is due to increased insulin secretion. 相似文献
992.
993.
SA Kliewer JT Moore L Wade JL Staudinger MA Watson SA Jones DD McKee BB Oliver TM Willson RH Zetterstr?m T Perlmann JM Lehmann 《Canadian Metallurgical Quarterly》1998,92(1):73-82
PURPOSE: To determine the effects of 28 d of creatine supplementation during training on body composition, strength, sprint performance, and hematological profiles. METHODS: In a double-blind and randomized manner, 25 NCAA division IA football players were matched-paired and assigned to supplement their diet for 28 d during resistance/agility training (8 h x wk[-1]) with a Phosphagen HP (Experimental and Applied Sciences, Golden, CO) placebo (P) containing 99 g x d(-1) of glucose, 3 g x d(-1) of taurine, 1.1 g x d(-1) of disodium phosphate, and 1.2 g x d(-1) of potassium phosphate (P) or Phosphagen HP containing the P with 15.75 g x d(-1) of HPCE pure creatine monohydrate (HP). Before and after supplementation, fasting blood samples were obtained; total body weight, total body water, and body composition were determined; subjects performed a maximal repetition test on the isotonic bench press, squat, and power clean; and subjects performed a cycle ergometer sprint test (12 x 6-s sprints with 30-s rest recovery). RESULTS: Hematological parameters remained within normal clinical limits for active individuals with no side effects reported. Total body weight significantly increased (P < 0.05) in the HP group (P 0.85 +/- 2.2; HP 2.42 +/- 1.4 kg) while no differences were observed in the percentage of total body water. DEXA scanned body mass (P 0.77 +/- 1.8; HP 2.22 +/- 1.5 kg) and fat/bone-free mass (P 1.33 +/- 1.1; HP 2.43 +/- 1.4 kg) were significantly increased in the HP group. Gains in bench press lifting volume (P -5 +/- 134; HP 225 +/- 246 kg), the sum of bench press, squat, and power clean lifting volume (P 1,105 +/- 429; HP 1,558 +/- 645 kg), and total work performed during the first five 6-s sprints was significantly greater in the HP group. CONCLUSION: The addition of creatine to the glucose/taurine/electrolyte supplement promoted greater gains in fat/bone-free mass, isotonic lifting volume, and sprint performance during intense resistance/agility training. 相似文献
994.
SJ Ander LM Blomkvist JC M?lne KJ Johansson SP Smeds 《Canadian Metallurgical Quarterly》1997,20(11):640-647
The morphology, cell proliferation and function of transplanted normal, hyperplastic and adenomatous human parathyroid tissue was studied after transplantation to athymic mice. The iPTH was evaluated in relation to morphology. Human parathyroid tissue collected during surgery for hyperparathyroidism was implanted subcutaneously into athymic mice (nu/nu-BALB/cA) and was analysed 1, 4, 7 and 12 weeks after transplantation. The transplants were examined by light and electron microscopy and by autoradiography after continuous infusion of 3H-thymidine. The relative amount of viable tissue was evaluated using a computer image analysing programme. Graft function was evaluated by measuring human iPTH in mouse serum. A transplant take ratio of 93% was observed. The proliferation rate in adenoma grafts at 12 weeks after transplantation was five and fifteen times that observed in normal and hyperplastic transplants, respectively. In normal and adenoma groups, a continuous increase in iPTH concentrations was observed, but in the hyperplastic group the iPTH remained on the same level. The secretion of iPTH in relation to the amount of transplanted tissue and the fraction of viable tissue was at the same level at 12 weeks in normal and adenomatous grafted animals. In conclusion, human parathyroid tissue was successfully transplanted and maintained its original structure. The growth potential, but not the iPTH secretion, was significantly higher in adenoma grafts compared to grafts from hyperplastic and normal glands. 相似文献
995.
For oxygenation of polyenoic fatty acids by 12- and 15-lipoxygenases the methyl terminus of the substrate constitutes the signal for the initial hydrogen abstraction. In contrast, for 5-lipoxygenases an inverse head to tail substrate orientation has been proposed. However, recent structure-based sequence alignments suggested a conserved uniform substrate orientation for 5S- and 15S-lipoxygenation. Oxygenation of 15S-HETE derivatives by various wild-type and mutant lipoxygenases was investigated, and the evidence proved an inverse substrate orientation: (i) Substrate affinity and Vmax of 15S-HETE oxygenation by arachidonic acid 15-lipoxygenases are >1 order of magnitude lower than the corresponding data for polyenoic fatty acids. 5S,15S- and 14R, 15S-DiH(P)ETE were identified as major reaction products. (ii) Methylation of the carboxylate group of 15S-HETE augmented the reaction rate and shifted the reaction specificity strongly toward 5S-lipoxygenation. In contrast, methyl arachidonate was less effectively oxygenated than the free acid. Methylation of 15S-HETrE(8,11,14), which lacks the C5-C6 double bond, was without major impact on the oxygenation rate and on the product specificity. (iii) Introduction of a bulky glycerol moiety at the carboxylic group of 15S-HETE reversed the kinetic effects of methylation and led to a 14R-oxygenation of the substrate. (iv) When the product pattern of 15S-HETE oxygenation by the recombinant wild-type rabbit 15-lipoxygenase was compared with that formed by the Arg403Leu mutant, 5S- and 8S-lipoxygenations were augmented and 14R, 15S-DiH(P)ETE formation was impaired. (v) Phe353Leu or Ile418Ala mutation of the same enzyme, which favored 12S-HETE formation from arachidonic acid, strongly augmented 8S-lipoxygenation of 15S-HETE methyl ester. These kinetic data and the alterations in the product specificity are consistent with the concept of an inverse head to tail substrate orientation during the oxygenation of 15S-HETE methyl ester and/or of free 15S-HETE by 15-LOXs. For 5S- and 8S-lipoxygenation, 15-HETE may slide into the substrate binding pocket with its carboxy terminus approaching the doubly allylic methylenes C-7 or C-10 to the non-heme iron. 相似文献
996.
Interest in measuring the quality of life (QL) in relation to health care has increased enormously in recent years. This is also true for end-stage renal failure where it is important not only to provide a better survival but also the quality of that survival. The aim of this study was to assess the relative influence of different kinds of treatment on end-stage renal disease after the patients' evaluation of their overall QL. We studied 167 patients receiving conservative treatment (45), haemodialysis (44), haemodialysis and erythropoieth (36), and continuous ambulatory peritoneal dialysis (42). The patients completed an original questionnaire consisting of 37 questions divided in five groups and generating 15 QL variables: personal data (name, gender, age, basic kidney disease); sociodemographic data influenced by the illness (family history, working ability, employment status); general health characteristics (fatigue, appetite, wound healing, sleep, resistance to cold); aspects of private life that are mostly influenced by the disease (social interaction, traveling, mood, sports, sexual life), and patients subjective assessment of their condition (self care and happiness). Patients on haemodialysis showed lower levels of QL than that on peritoneal dialysis related to fatigue (p < 0.01), working ability (p < 0.05), wound healing (p < 0.05), and appetite (p < 0.01) compared to the conservative treatment. Peritoneal dialysis had also a statistically significant positive influence on fatigue (p < 0.05) compared to conservative treatment. However, erythropoletin treatment showed better results with regard to traveling (p < 0.05), resistance to cold (p < 0.01), self care (p < 0.05) and mood (p < 0.05) compared to peritoneal dialysis, and working ability (p < 0.05), fatigue (p < 0.05) and mood (p < 0.05) compared to conservative treatment and haemodialysis. 相似文献
997.
Lysophosphatidylcholine (LPC) is formed by hydrolysis of PC in low density lipoprotein (LDL) and cell membranes by phospholipase A2 or by oxidation. Oxidized (ox) LDL activates endothelial cells, an effect mimicked by LPC. oxLDL also has the capacity to activate T and B cells, and antibody titers to oxLDL are related to the degree of atherosclerosis. The antigen in oxLDL responsible for its immune-stimulatory capacity is not well characterized, and we hypothesized that LPC was involved. We demonstrate herein the presence of antibodies against LPC, both of the IgG and IgM isotype, in 210 healthy individuals. This antibody reactivity was not specifically related to oxidation of the fatty acid moiety in LPC, since LPC containing only palmitic acid showed antibody titers equivalent to those of LPC containing unsaturated fatty acids. Antibody titers to PC were low compared with LPC, and hydrolysis of PC at the sn-2 position is thus essential for immune reactivity. There was a close correlation between anti-oxLDL and anti-LPC antibodies. Furthermore, LPC competitively inhibited anti-oxLDL reactivity, which indicates that LPC may explain a significant part of the immune-stimulatory properties of oxLDL. LPC, being a lipid, is not likely to be an antigen itself. Instead, LPC could form immunogenic complexes with peptides, which may induce and potentiate immune reactions in the vessel wall. This study adds to the evidence that LPC is an important component of oxLDL and emphasizes the potential role of phospholipase A2 in atherosclerosis. 相似文献
998.
999.
The cell cycle regulatory proteins, which include cyclin-dependent kinases (cdks), cdk inhibitors (CKIs), cyclins, and the pRB, and E2F families of proteins, constitute a network of interacting factors which govern exit from or passage through the mammalian cell cycle. While the proteins within these families have similar structural characteristics, each family member exhibits distinct expression patterns during embryogenesis and distinct biological activities. In order to begin to understand the tissue-specific roles of these interacting factors, we determined the expression pattern and activity of the pRB, E2F, cyclin, cdk, and CKI families of cell cycle regulatory proteins during retinoic acid-induced (neuronal pathway) and DMSO-induced (cardiac muscle pathway) differentiation of the pluripotent murine embryonal carcinoma cell line, P19. We demonstrate here that P19 terminal differentiation causes lineage-specific changes in the expression and activity of distinct members of the E2F, pRB, cyclin, and CKI families. Furthermore, dynamic changes in the activities of these cell cycle regulatory proteins occur through several overlapping mechanisms, culminating in repression of DNA-binding activity by all of the E2F family members as cells terminally differentiate. 相似文献
1000.