全文获取类型
收费全文 | 1258篇 |
免费 | 0篇 |
专业分类
综合类 | 1篇 |
化学工业 | 4篇 |
建筑科学 | 1篇 |
水利工程 | 1篇 |
武器工业 | 1篇 |
一般工业技术 | 6篇 |
冶金工业 | 1241篇 |
自动化技术 | 3篇 |
出版年
2014年 | 1篇 |
2013年 | 2篇 |
2011年 | 3篇 |
2010年 | 1篇 |
2009年 | 1篇 |
2007年 | 1篇 |
2006年 | 1篇 |
2005年 | 1篇 |
2004年 | 2篇 |
2003年 | 2篇 |
2000年 | 2篇 |
1999年 | 40篇 |
1998年 | 397篇 |
1997年 | 246篇 |
1996年 | 157篇 |
1995年 | 69篇 |
1994年 | 59篇 |
1993年 | 85篇 |
1992年 | 12篇 |
1991年 | 16篇 |
1990年 | 11篇 |
1989年 | 9篇 |
1988年 | 9篇 |
1987年 | 11篇 |
1986年 | 14篇 |
1985年 | 13篇 |
1983年 | 2篇 |
1982年 | 5篇 |
1981年 | 7篇 |
1980年 | 8篇 |
1978年 | 3篇 |
1977年 | 16篇 |
1976年 | 50篇 |
1975年 | 1篇 |
1955年 | 1篇 |
排序方式: 共有1258条查询结果,搜索用时 15 毫秒
991.
OBJECTIVE: There are few data on urinary markers of collagen breakdown in children. We have determined a normal range for urinary pyridinoline and deoxypyridinoline in children, assessed the variability in excretion in individual children and examined the effect of GH treatment on the excretion of these collagen cross-links. DESIGN: A cross-sectional study of a group of healthy children and sequential samples from children receiving GH treatment. PATIENTS: One hundred and nine healthy children aged 2-15 years, 8 healthy children aged 4-11 years and 4 children receiving GH treatment. MEASUREMENTS: Total pyridinoline and deoxypyridinoline excretion were measured by high performance liquid chromatography after initial acid hydrolysis and cellulose extraction steps. Serum parathyroid hormone was measured using a two-site immunoradiometric assay and urinary hydroxyproline by Ehrlich's reaction using a colorimetric assay. Pyridinoline and deoxypyridinoline excretion were expressed as a ratio against urine creatinine. RESULTS: High excretion of pyridinoline (Pyr) and deoxypyridinoline (DPyr) was seen at all ages with no apparent relation to age (mean Pyr/Cr 115 nmol/mmol and DPyr/Cr 31 nmol/mmol). No correlation was found with serum parathyroid hormone or urinary hydroxyproline excretion. Marked day to day variation was seen in individual children. A progressive rise in excretion was seen in children receiving GH treatment with no significant correlation to height velocity. CONCLUSIONS: There is a high excretion of the pyridinium cross-linking amino acids in children of all ages compared to adults. However, a high variability exists in single morning urine samples which will limit the usefulness of these markers in growing children. 相似文献
992.
993.
NJ Harmat R Giorgi F Bonaccorsi G Cerbai SM Colombani AR Renzetti R Cirillo A Subissi G Alagona C Ghio 《Canadian Metallurgical Quarterly》1995,38(15):2925-2937
A series of N-[biphenylyl(tetrazolyl)methyl]-2-butylimidazoles containing variously substituted diazine or pyridine moieties either as their free bases or N-oxide derivatives attached to the 4-position of the imidazole ring was synthesized and tested for interaction with the AT1 receptors of rat adrenal cortex membranes (receptor binding assay). Some compounds were then chosen for further evaluation in vivo in the A II-induced pressor response in conscious normotensive rats. The most potent in the AT1 binding assay were found to be compounds in which the diazine or pyridine ring nitrogen is adjacent to the point of attachment between the two heteroaromatic rings such as 2-butyl-4-(3,6-dimethylpyrazin-2-yl)-1-[[2'-(1H-tetrazol-5-y l)-biphenyl-4- yl]methyl]-1H-imidazole (3b) or 2-butyl-4-[5-(methoxycarbonyl)pyrid-2-yl]-1-[[2'-(1H-tetrazol++ +-5- yl)biphenyl-4-yl]methyl]-1H-imidazole (6c). The binding affinities and oral activities of the pyridine N-oxide imidazoles in which a stabilizing group ortho to the pyridine ring nitrogen is present were markedly improved as in 2-butyl-4-[(3-methoxycarbonyl)-6-methyl-N-oxopyridin-2-yl]-1-[[2'- (1H- tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-imidazole 31b. Molecular modeling studies were carried out to determine the molecular electrostatic potential values of related model systems and to correlate their receptor interaction energies with the observed activities of our compounds. 相似文献
994.
995.
996.
NJ Broom JS Elder PC Hannan JE Pons PJ O'Hanlon G Walker J Wilson P Woodall 《Canadian Metallurgical Quarterly》1995,48(11):1336-1344
Semisynthetic analogues of pseudomonic acid A have been prepared containing a heterocyclyl substituted oxazole. Derivatives in which the heterocycle was thiophene, furan, pyridine, or isoxazole showed good antibacterial potency and were further evaluated in vivo. Both pharmacokinetic parameters and oral activity against an experimental intraperitoneal sepsis were superior to results obtained from previously described pseudomonic acid A derivatives. 相似文献
997.
NJ Chalupny A Aruffo JM Esselstyn PY Chan J Bajorath J Blake LK Gilliland JA Ledbetter MA Tepper 《Canadian Metallurgical Quarterly》1995,25(10):2978-2984
CD19 is a B cell surface protein capable of forming non-covalent molecular complexes with a number of other B cell surface proteins including the CD21/CD81/Leu-13 complex as well as with surface immunoglobulin. CD19 tyrosine phosphorylation increases after B cell activation, and is proposed to play a role in signal transduction through its cytoplasmic domain, which contains nine tyrosine residues. Several second messenger proteins have been shown to immunoprecipitate with CD19, including p59 Fyn (Fyn), p59 Lyn (Lyn) and phosphatidylinositol-3 kinase (PI-3 kinase). These associations are predicted to occur via the src-homology 2 (SH2) domains of the second messenger proteins. Two of the cytoplasmic tyrosines in the CD19 cytoplasmic region contain the consensus binding sequence for the PI-3 kinase SH2 domain (YPO4-X-X-M). However, the reported consensus binding sequence for the Fyn and Lyn SH2 domains (YPO4-X-X-I/L) is not found in CD19. We investigated the capacity of CD19 cytoplasmic tyrosines to bind both Fyn and PI-3 kinase SH2-domain fusion proteins. In activated B cells, both Fyn and PI-3 kinase SH2-domain fusion proteins precipitate CD19. Using synthetic tyrosine-phosphorylated peptides comprising each of the CD19 cytoplasmic tyrosines and surrounding amino acids, we investigated the ability of the Fyn SH2 and PI-3 kinase SH2 fusion proteins to bind to the different CD19 cytoplasmic phosphotyrosine peptides. ELISA revealed that the two CD19 cytoplasmic tyrosine residues contained within the Y-X-X-M sequences (Y484 and Y515) bound preferentially to the PI-3 kinase SH2-domain fusion proteins. Two different tyrosines (Y405 and Y445) bound preferentially to the Fyn SH2-domain fusion protein via a novel sequence, Y-E-N-D/E, different from that previously reported for the Fyn SH2 domain. In precipitation studies, peptide Y484 was able to compete with tyrosine phosphorylated CD19 specifically for binding to the PI-3 kinase SH2 domain fusion proteins, while peptides Y405 and Y445 were able to compete specifically for binding to the Fyn SH2 domain fusion proteins. These results indicate that CD19 may be capable of binding both Fyn and PI-3 kinase concurrently, suggesting a mechanism for CD19 signal transduction, in which binding of PI-3 kinase to the Fyn SH3 domain results in activation of PI-3 kinase. 相似文献
998.
999.
1000.
RC Wilmouth NJ Westwood K Anderson W Brownlee TD Claridge IJ Clifton GJ Pritchard RT Aplin CJ Schofield 《Canadian Metallurgical Quarterly》1998,37(50):17506-17513
beta-Lactam inhibitors of transpeptidase enzymes involved in cell wall biosynthesis remain among the most important therapeutic agents in clinical use. beta-Lactams have more recently been developed as inhibitors of serine proteases including elastase. All therapeutically useful beta-lactam inhibitors operate via mechanisms resulting in the formation of hydrolytically stable acyl-enzyme complexes. Presently, it is difficult to predict which beta-lactams will form stable acyl-enzyme complexes with serine enzymes. Further, the factors that result in the seemingly special nature of beta-lactams versus other acylating agents are unclear-if indeed they exist. Here we present the 1.6 A resolution crystal structure of a stable acyl-enzyme complex formed between porcine pancreatic elastase and a representative monocyclic beta-lactam, which forms a simple acyl-enzyme. The structure shows that the ester carbonyl is not located within the oxyanion hole and the "hydrolytic" water is displaced. Combined with additional kinetic and mass spectrometric data, the structure allows the rationalization of the low degree of hydrolytic lability observed for the beta-lactam-derived acyl-enzyme complex. 相似文献