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901.
902.
903.
Pre-column derivatization with o-phthaldialdehyde and an optically active thiol has hitherto been used mainly for liquid-chromatographic chiral separation of amino acids. Chiral separation of non-amino-acid primary amines, especially of pharmaceuticals, via this approach has been largely ignored. We have therefore examined the applicability of the method to the chiral resolution of several pharmaceutical amines. o-Phthaldialdehyde and four commercially available homochiral thiols were used to study the separation of the enantiomers of amphetamine, p-hydroxyamphetamine, p-chloroamphetamine, 3-amino- 1-phenylbutane, 3-amino-1-(4-hydroxyphenyl)-butane, mexiletine, tocainide, tranylcypromine and rimantadine. The resulting highly fluorescent isoindole derivatives were resolved on a Waters Nova-Pak C18 column using mobile phases consisting of mixtures of methanol, a sodium acetate buffer and acetonitrile, and the column effluent was monitored using fluorescence or UV detection. In some cases the fluorescence and/or the UV absorbance of the two diastereomers were unequal. It was found that the resolution of most of the amines could be optimized by varying the homochiral thiol in the derivatization step. This method of chiral separation may have wide applicability in enantiospecific drug analysis of non-amino-acid primary amines due to its simplicity and the high sensitivity it provides. 相似文献
904.
905.
Research on membrane complement inhibitors (DAF, MCP, and CD59) has led to understanding of the regulation of complement system; however, their precise role and distribution remain speculative. In this study, we used an indirect fluorescent immunostaining to investigate the distribution of complements, MCP, DAF, and CD59, in the villi before the 10th week of pregnancy in 18 women. DAF and MCP were observed at the surface of syncytiotrophoblasts (ST) and extravillous trophoblast (EVT) in all subjects. They were observed in villous cytotrophoblast (VCT) in the subjects before the 8th week of pregnancy but were not observed in any subject after the 9th week. However, CD59 appeared in ST but never in VCT. MCP, DAF, and CD59 were observed in EVT. These findings indicated that these complement inhibitors played an important role in early pregnancy, and that CD59 continued to appear in early pregnancy, whereas the expression of MCP and DAF depended on the stage of pregnancy. 相似文献
906.
Multiple mechanisms in the long-QT syndrome. Current knowledge, gaps, and future directions. The SADS Foundation Task Force on LQTS 总被引:1,自引:0,他引:1
DM Roden R Lazzara M Rosen PJ Schwartz J Towbin GM Vincent 《Canadian Metallurgical Quarterly》1996,94(8):1996-2012
The congenital long-QT syndrome (LQTS) is characterized by prolonged QT intervals, QT interval lability, and polymorphic ventricular tachycardia. The manifestations of the disease vary, with a high incidence of sudden death in some affected families but not in others. Mutations causing LQTS have been identified in three genes, each encoding a cardiac ion channel. In families linked to chromosome 3, mutations in SCN5A, the gene encoding the human cardiac sodium channel, cause the disease, Mutations in the human ether-à-go-go-related gene (HERG), which encodes a delayed-rectifier potassium channel, cause the disease in families linked to chromosome 7. Among affected individuals in families linked to chromosome 11, mutations have been identified in KVLQT1, a newly cloned gene that appears to encode a potassium channel. The SCN5A mutations result in defective sodium channel inactivation, whereas HERG mutations result in decreased outward potassium current. Either mutation would decrease net outward current during repolarization and would thereby account for prolonged QT intervals on the surface ECG. Preliminary data suggest that the clinical presentation in LQTS may be determined in part by the gene affected and possibly even by the specific mutation. The identification of disease genes in LQTS not only represents a major milestone in understanding the mechanisms underlying this disease but also presents new opportunities for combined research at the molecular, cellular, and clinical levels to understand issues such as adrenergic regulation of cardiac electrophysiology and mechanisms of susceptibility to arrhythmias in LQTS and other settings. 相似文献
907.
X Fan DM Biskobing D Fan W Hofstetter J Rubin 《Canadian Metallurgical Quarterly》1997,12(9):1387-1395
Macrophage colony-stimulating factor (MCSF), although necessary for entry of precursors into the early preosteoclast pathway, inhibits osteoclastogenesis at high doses. To clarify the relationship between MCSF and osteoclast formation, we investigated the effect of exogenous MCSF in murine bone marrow culture. Precursor proliferation and the expression of MCSF-receptor were examined after 4 days of culture in the presence or absence of accessory stromal cells. In both mixed marrow and destromalized cell cultures, exogenous MCSF dose-dependently decreased 125I-MCSF binding (by 65 +/- 5.0% at 3500 and 87 +/- 16.7% at-7000 U/ml, respectively) while enhancing mononuclear cell proliferation after 3 days of exposure (by 2.8- and 6.3-fold, respectively). These effects were maintained 24 h after removal of exogenous MCSF and, as such, likely represented an MCSF-induced change in MCSF receptor-bearing cells. Exposure to exogenous MCSF (3500 U/ml) days 2-4 dose-dependently inhibited tartrate resistant acid phosphatase positive multinuclear cell (TRAP+ MNC) formation counted at the end of day 7, by 64.3 +/- 4.1%. This inhibition of TRAP+ MNC formation was preceded by a 92 +/- 9% decrease in the expression of carbonic anhydrase II mRNA measurable at 4 days. These results indicate that MCSF promotes proliferation of a population of cells expressing lower cognate receptor sites. Changes in MCSF-receptor expression appear to modulate the final lineage selection of the pluripotent monoblastic progenitor. 相似文献
908.
Pentachlorophenol (PCP), which has been used as a wood preservative, was reported to be a liver carcinogen in mice. To investigate the initial effects of PCP administration under the same conditions of exposure as in the carcinogenic study, we examined oxidative stress and cell proliferation, along with other hepatotoxicological parameters, in the livers of B6C3F1 mice fed PCP in their diet at doses of 0.03, 0.06, and 0.12% for up to 4 weeks. We observed significant increases of 8-OHdG levels in hepatic nuclear DNA at doses of 0.03% and above at 2 and 4 weeks. Likewise, dose-dependent increases in the labeling index of cells were detected by counting those that had incorporated 5-bromo-2'-deoxyuridine throughout the experimental period. Also, we found significant elevations of the liver weights, concurrent with increases in hepatic DNA content in the treated mice, which again were dose-related. Serum aspartic transferase activity at doses of 0.06% and above were significantly increased despite these changes being slight. Also, histopathological examination provided no evidence of necrotic changes, but severe hepatocyte swelling in the treated mouse livers. These data indicate that PCP might be able to induce cell proliferation in the mouse liver, as well as induce oxidative DNA damage, suggesting both changes may play an important role in hepatocarcinogenesis. 相似文献
909.
HE Grossniklaus DM Albert WR Green BP Conway KR Hovland 《Canadian Metallurgical Quarterly》1997,115(7):894-898
OBJECTIVE: To describe 2 enucleated eyes of patients enrolled in the Collaborative Ocular Melanoma Study that contained primary choroidal melanoma with clear cell features. METHODS: During a 9-year period, 1493 eyes enucleated as part of the Collaborative Ocular Melanoma Study routinely processed for histologic examination were evaluated by the pathology review committee (H.E.G, D.M.A, and W.R.G). Two eyes with unusual variants of choroidal melanoma were identified and immunostained for S100 protein and HMB 45. Portions of the tumors were processed for electron microscopic examination. RESULTS: Results of electron microscopic examination of both tumors displayed malignant melanoma (mixed cell type with many malignant cells with clear cytoplasm). The cytoplasm of the clear cells stained with periodic acid-Schiff and failed to stain when pretreated with diastase. Results of immunohistochemical stains in both tumors were positive for S100 protein and HMB 45 in the tumor cells. Results of electron microscopic examination showed that the cytoplasm of the clear cells contained scattered glycogen granules, premelanosomes, and melanosomes. CONCLUSION: These cases represent a clear cell variant of malignant melanoma of the choroid. This tumor should not be confused with metastatic clear cell carcinoma to the choroid. 相似文献
910.
DM Roden 《Canadian Metallurgical Quarterly》1993,72(4):51A-55A
Two trial designs have been used in evaluating sotalol in patients with sustained tachyarrhythmias: open-label dose escalation and randomized comparison with reference agents. At least 7 open-label studies (n = 16-65) have been reported from single centers in patients in whom trials of numerous other antiarrhythmic agents were unsuccessful. At the doses used, usually 320-640 mg/day, plasma concentrations were in the range associated with both beta blockade and class III antiarrhythmic activity (2-3 micrograms/mL). These concentrations produced electrophysiologic changes that were consistent across studies: 10-16% increase in right ventricular effective refractory period (ERP), 4-8% increase in corrected QT interval (QTc), and 17-30% increase in sinus cycle length (corresponding to a 15-23% decrease in heart rate). In these open-label trials, sotalol suppressed inducible ventricular tachyarrhythmias in 20-72% of patients; the higher degrees of efficacy were reported when induction protocols were confined to double extrastimuli. Side effects leading to discontinuation of sotalol in patients with sustained ventricular tachycardia or fibrillation include fatigue (4.0%), marked bradycardia (3.0%), torsades de pointes (3.0%), and heart failure or pulmonary edema (1.0%). A multicenter randomized trial compared intravenous sotalol with intravenous procainamide in a double-blind prospective fashion. Sotalol suppressed ventricular tachyarrhythmias inducible with triple extrastimuli in 15 (30%) of 50 patients, whereas procainamide was effective in 10 (20%) of 50. In this and other series, responsiveness to sotalol was prospectively identified by a particularly fast tachycardia at baseline (e.g., cycle length of < 270 msec), but not by the extent of changes in global indices of repolarization (QTc, ERP).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献