全文获取类型
收费全文 | 841篇 |
免费 | 4篇 |
国内免费 | 1篇 |
专业分类
电工技术 | 2篇 |
化学工业 | 40篇 |
金属工艺 | 3篇 |
机械仪表 | 5篇 |
建筑科学 | 3篇 |
能源动力 | 23篇 |
轻工业 | 27篇 |
水利工程 | 2篇 |
无线电 | 15篇 |
一般工业技术 | 61篇 |
冶金工业 | 632篇 |
原子能技术 | 4篇 |
自动化技术 | 29篇 |
出版年
2023年 | 3篇 |
2022年 | 4篇 |
2021年 | 10篇 |
2019年 | 4篇 |
2018年 | 9篇 |
2017年 | 7篇 |
2016年 | 5篇 |
2015年 | 3篇 |
2014年 | 4篇 |
2013年 | 20篇 |
2012年 | 12篇 |
2011年 | 12篇 |
2010年 | 9篇 |
2009年 | 11篇 |
2008年 | 10篇 |
2007年 | 8篇 |
2006年 | 5篇 |
2005年 | 9篇 |
2004年 | 7篇 |
2003年 | 4篇 |
2002年 | 5篇 |
2001年 | 6篇 |
2000年 | 3篇 |
1999年 | 24篇 |
1998年 | 165篇 |
1997年 | 107篇 |
1996年 | 74篇 |
1995年 | 47篇 |
1994年 | 37篇 |
1993年 | 37篇 |
1992年 | 6篇 |
1991年 | 7篇 |
1990年 | 8篇 |
1989年 | 8篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1983年 | 3篇 |
1982年 | 8篇 |
1981年 | 8篇 |
1980年 | 9篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 39篇 |
1976年 | 48篇 |
1975年 | 4篇 |
1973年 | 2篇 |
1969年 | 2篇 |
1955年 | 2篇 |
排序方式: 共有846条查询结果,搜索用时 15 毫秒
81.
C Lazure D Gauthier F Jean A Boudreault NG Seidah HP Bennett GN Hendy 《Canadian Metallurgical Quarterly》1998,273(15):8572-8580
The cleavage of parathyroid hormone (PTH) from its precursor proparathyroid hormone (pro-PTH) is accomplished efficiently by the proprotein convertase furin (Hendy, G. N., Bennett, H. P. J., Gibbs, B. F., Lazure, C., Day, R., and Seidah, N. G. (1995) J. Biol. Chem. 270, 9517-9525). We also showed that a synthetic peptide comprising the -6 to +7 sequence of human pro-PTH is appropriately cleaved by purified furin in vitro. The human pro-PTH processing site Lys-Ser-Val-Lys-Lys-Arg differs from the consensus furin site Arg-Xaa-(Lys/Arg)-Arg that is represented by Arg-Arg-Leu-Lys-Arg in the cleavage site of pro-PTH-related peptide (pro-PTHrP). An earlier study demonstrated that an internally quenched fluorogenic substrate bearing an O-aminobenzoyl fluorescent donor at the NH2 terminus and an acceptor 3-nitrotyrosine near the COOH terminus was appropriately cleaved by the convertases furin and PC1 (Jean, F., Basak, A., DiMaio, J., Seidah, N. G., and Lazure, C. (1995) Biochem. J. 307, 689-695). Here, we have synthesized a series of internally quenched fluorogenic substrates based upon the pro-PTH and pro-PTHrP sequences to determine which residues are important for furin cleavage. Purified recombinant furin and PC1 cleaved the human pro-PTH internally quenched substrate at the appropriate site in an identical manner to that observed with the nonfluorescent peptide. Several substitutions in the P6-P3 sequence were well tolerated; however, replacement of the Lys at the P6 position with Gly and replacement of the P3 Lys by an acidic residue led to markedly compromised cleavage by furin. Furin activity was very sensitive to substitution in P' positions. Replacement of Ser at P1' with Gly and Val at P2' with Ala generated substrates that were less well cleaved. Substitution at the P1' position of Val for Ser in conjunction with Ala for Val at P2', as well as a single substitution of Lys for Val at P2', generated specific inhibitors of furin cleavage. The findings of this study open the way to the rational design of inhibitors of furin with therapeutic potential. 相似文献
82.
1-Nitropyrene (1-NP), the predominant nitropolycyclic hydrocarbon found in diesel exhaust, is a mutagen and tumorigen. Nitroreduction is a major pathway by which 1-NP is metabolized. Reductively activated 1-NP forms a major DNA adduct, N-(deoxyguanosin-8-yl)-1-aminopyrene (dGAP), both in vitro and in vivo. In Salmonella typhimurium 1-NP induces a CpG deletion in a CGCGCGCG sequence. In Escherichia coli, however, mostly -1 and +1 frame-shifts are observed, which occur predominantly in 5'-CG, 5'-GC, and 5'-GG sequences. In order to determine the mechanism of mutagenesis by dGAP in a CpG repetitive sequence, we constructed a single-stranded M13 genome containing the adduct at the underscored deoxyguanosine of an inserted CGCGCG sequence. In E. coli strains with normal repair capability the adduct induced approximately 2% CpG deletions, which was 20-fold that of the control. With SOS, the frequency of frame-shift mutations increased to 2.6%, even though the frequency of CpG deletion accompanied 50% reduction. The enhancement in mutagenesis was due to a +1 frame-shift that occurred at a high frequency. In strains with a defect in methyl-directed mismatch repair, 50-70% increase in mutation frequency was observed. When these strains were SOS induced, frame-shift mutagenesis increased by approximately 100%. When transfections were carried out in dnaQ strains that are impaired in 3'-->5'exonuclease activity of DNA polymerase III, frame-shift mutagenesis increased 5-7-fold. dGAP-induced frame-shifts in the (CG)3 sequence, therefore, varied from 2% to 17% depending on the state of repair of the host cells. We conclude that dGAP induces both -2 and +1 frame-shifts in a CpG repetitive sequence and that these two mutagenic events are competing pathways. The CpG deletion does not require SOS functions, whereas the +1 frame-shifts are SOS-dependent. On the basis of the data in repair-deficient strains, it appears that both types of frame-shifts occurred as a result of misalignment, which are corrected primarily by the proofreading exonuclease of the DNA polymerase. Misaligned structures that escape the exonuclease are repaired by the methyl-directed mismatch repair, albeit with limited efficiency. 相似文献
83.
AIu Egorov LM Garmashova IV Lukashok GN Nevedomskaia GI Aleksandrova AI Klimov 《Canadian Metallurgical Quarterly》1994,39(5):201-205
Phenotypical properties of single-gene reassortants of attenuated cold-adapted strain A/Leningrad/135/47/57 (H2N2) and strain A/PR8/34 virulent for laboratory animals were studied. Only the group of reassortants inheriting NS gene from cold-adapted virus was fully attenuated for various animals species, similarly as reassortants with 6/2 genomic formula containing all the 6 internal protein genes from strain A/Leningrad/134/47/57. Reassortant 25A-1 single-gene for NS was temperature-sensitive (ts) on mammalian cells but formed plaques at 40 degrees C on chicken kidney cells. Reassortants with genomic formula 6/2 were temperature-sensitive in all types of cells used. Reassortant 25A-1 could synthesize normal amounts of polypeptides in MDCK cells at 39 degrees C, whereas protein synthesis of reassortants with 6/2 genomic formula was noticeably reduced at this temperature. Hence, a similar level of attenuation of both reassortant groups appears to be due to various molecular mechanisms. Possible role of NS2 gene mutation in attenuation of strain A/Leningrad/134/47/57 and its reassortants is discussed. 相似文献
84.
KN Wright T Morley J Bicknell SP Bishop GP Walcott GN Kay 《Canadian Metallurgical Quarterly》1998,9(9):976-984
INTRODUCTION: Permanent cure of reentrant ventricular tachycardia (VT) associated with coronary artery disease is difficult to achieve. Retrograde coronary venous infusion of ethanol for ablation of ventricular myocardium associated with reentrant tachyarrhythmias has several potential advantages, including use of physiologic mapping techniques and production of deeper, wider necrotic zones. METHODS AND RESULTS: Nine anesthetized dogs had baseline hemodynamic measurement, left ventriculography, coronary arteriography, occlusive coronary venography, and programmed electrical stimulation of the right ventricular apex and outflow tract. A balloon-tipped infusion catheter was advanced into a distal coronary venous branch, the balloon slowly inflated, and pure ethanol infused at volumes of 1.5, 3, or 5 cc. Hemodynamic measurements, angiography, ventriculography, and programmed electrical stimulation were repeated immediately and 1 week following ablation. Formalin-perfused hearts were serially sectioned and lesion volumes determined. Histologic examination of ablation beds then was performed. No significant difference was found in any hemodynamic measurement before or after ablation. Coronary arteriograms and left ventriculograms were unchanged after ablation. Nonsustained VT occurred in eight dogs during ethanol infusion; however, VT was not inducible in any dog before or after ablation. Infusion volumes of 3 cc or more were required to produce transmural lesions. CONCLUSION: Retrograde coronary venous infusions of ethanol using a balloon-tipped infusion catheter were effective in ablating ventricular myocardium. Retrograde chemical ablation did not itself result in inducible VT or adversely affect hemodynamic measurements or coronary arteries. Transmural myocardial necrosis, necessary in the ablation of VT associated with coronary artery disease, can be produced by higher infusion volumes. 相似文献
85.
An insulin delivery system based on liquid surfactant membranes has been developed. The formulation was based on a w/o/w emulsion where an organic membrane separated two aqueous phases and the internal aqueous phase contained insulin. Sesame and cotton seed oils were used as organic membranes. In order to facilitate the transportation of glucose across the organic membrane various additives such as calcium stearate, lecithin, cholesterol, hexamine, stearic acid and glyceryl tristearate were used. The additives were found to be successful carriers for the transportation of glucose to the internal aqueous phase. Similarly, viscosity enhancers, e.g. cetostearyl alcohol, in the organic phase enhanced the immobilization of insulin. Various parameters affecting the stability of the emulsions were established. The developed system was characterized for insulin activity and insulin efflux profile. 相似文献
86.
NK Karamanos P Vanky GN Tzanakakis T Tsegenidis A Hjerpe 《Canadian Metallurgical Quarterly》1997,765(2):169-179
Rats deficient in vitamin A express low levels of P4502C7 mRNA in the liver. Administration of all-trans retinoic acid (at-RA) or growth hormone (GH) to deficient animals only partially restored the expression whereas the combined treatment returned the P4502C7 mRNA levels to that observed in normal rats. That a retinoid is the predominant inducer of P4502C7 at the cellular level is evident from studies performed with primary hepatocytes, but it became clear that GH is a prerequisite for the vitamin A effect in vivo. The at-RA induction of P4502C7 mRNA in primary rat hepatocytes was inhibited by ketoconazole, an inhibitor of P450 activity, and by cycloheximide, blocking ongoing protein synthesis. In contrast, the at-RA induction of RAR-beta2 mRNA was not affected by any of these compounds. This could indicate previously not recognized mechanisms of at-RA action. Interestingly, at-4-oxo-RA, an at-RA metabolite formed by a P450 catalyzed reaction, also induced P4502C7 mRNA. Induction of P4502C7 mRNA by the retinoic acid receptor (RAR) selective agonist TTNPB indicated that this pathway is preferred over the retinoid X receptor (RXR) pathway. In addition, analysis of RA metabolites in liver cell extracts revealed the formation of several as yet unidentified metabolites. The formation of some of these metabolites was inhibited by ketoconazole and they could therefore constitute potential inducers of CYP2C7. We suggest that metabolism of at-RA, possibly by a P450 enzyme, is an important step in the at-RA induction of P4502C7. 相似文献
87.
Central hemodynamics was studied by thermodilution in 16 patients with acquired mitral defect during surgery under conditions of hypothermia without perfusion. Cooling and surgical correction were carried out under superficial ether anesthesia with morphine and droperidol. A 28% decrease of the minute circulation volume is observed as early as under general anesthesia and at the very beginning of cooling (10.8% more); this decrease is caused by rarer heart contractions and increase of the total peripheral vascular resistance as a result of body response to cool exposure. An almost 10 degrees C drop of body temperature (to 27.2 +/- 0.2 degrees C) involves a just 13% decrease of the cardiac index in comparison with the value at the beginning of cooling. Injection of droperidol before cooling blocks the increase of the total peripheral resistance in a dose-dependent mode (about 0.13 mg/kg of droperidol is needed for sufficiently complete prevention of the increase of total peripheral resistance), and thus maintains the stroke and cardiac indexes at a sufficiently high level. Morphine (in doses of up to 2.3 mg/kg) did not bring about such an effect. 相似文献
88.
89.
Development and characterization of pseudolatex based transdermal drug delivery system of diclofenac. 总被引:1,自引:0,他引:1
Suresh P. Vyas Partha Jyoti Gogoi Sanjay K. Jain 《Drug development and industrial pharmacy》1991,17(8):1041-1058
A transdermal drug delivery system of diclofenac was developed for prolonged and controlled release of diclofenac. The designed system essentially based on polymeric pseudolatex dispersion. The formulation variables that could effect the formulation stability vis a vis drug release were studied. To achieve the desired release rate, different combination of hydrophilic and hydrophobic polymer were used for the preparation of pseudolatex system. The designed system exhibited linear relationship between drug release (Q) V/s square root of time (t0.5). The product having skin permeability rate 0.188 mg/h/cm was selected for the in vitro anti-inflammatory activity and in vivo evaluation. The system could maintained a constant and effective plasma level for 24 hours. The effective drug plasma concentration was monitored periodically. The study revealed that designed pseudolatex transdermal drug delivery system of diclofenac could be used successfully with improved performance and hold promise for further studies. 相似文献
90.
A. Dhawan S. P. Vyas N. K. Jain K. C. Varma 《Drug development and industrial pharmacy》1991,17(16):2229-2237
Albumin microspheres containing actinomycin D were prepared by the heat stabilization method. The compata-bility of the drug with magnetite and the optimum stability of the drug in different pH were studied. Drug loaded albumin microspheres containing magnetite showed good magnetic response. Release of the drug was slow and continued for 7 days exhibiting sustained release property. The difference as regards to the size, shape, drug content and release rate from freshly prepared and freeze dried drug loaded albumin microspheres was negligible. 相似文献