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131.
CM Kam JE Kerrigan RR Plaskon EJ Duffy P Lollar FL Suddath JC Powers 《Canadian Metallurgical Quarterly》1994,37(9):1298-1306
A series of 7-amino-4-chloro-3-(3-isothioureidopropoxy)isocoumarin (NH2-CiTPrOIC) derivatives with various substituents at the 7- and 3-positions have been synthesized as inhibitors of several blood coagulation enzymes. Isocoumarins substituted with basic groups such as guanidino or isothioureidoalkoxy groups were previously shown to be potent irreversible inhibitors of blood coagulation enzymes [Kam et al. Biochemistry 1988, 27, 2547-2557]. Substituted isocoumarins with an isothioureidoethoxy group at the 3-position and a large hydrophobic group at the 7-position are better inhibitors for thrombin, factor VIIa, factor Xa, factor XIa, factor IIa, and factor IXa than NH2-CiTPrOIC (4). PhNHCONH-CiTEtOIC (14), (S)-Ph(CH3)CHNHCONH-CiTEtOIC (25), and (R)-Ph(CH3)CHNHCONH-CiTEtOIC (26) inhibit thrombin quite potently and have kobs/[I] values of (1-4) x 10(4) M-1 s-1. Modeled structures of several isocoumarins noncovalently complexed with human alpha-thrombin suggest that H-bonding between the 7-substituent and the Lys-60F NH3+ relates to the inhibitory potency. Thrombin inhibited by 14, 25, or 26 is quite stable, and only 4-16% of enzymatic activity is regained after incubation for 20 days in 0.1 M Hepes, pH 7.5 buffer. However, 100, 67, and 65% of enzyme activity, respectively, is regained with the addition of 0.38 M hydroxylamine. With normal citrated pig or human plasma, these isocoumarin derivatives prolong the prothrombin time ca. 1.3-3.1-fold and also prolong the activated partial thromboplastin time more than 3-7-fold at 32 microM. Thus, these compounds are effective anticoagulants in vitro and may be useful in vivo. 相似文献
132.
Epidermal spinous and granular cells from the newborn rat neither replicate their nuclear DNA nor proliferate in vitro under conditions which support both processes in basal cells. However, as shown by autoradiography, (3H)thymidine and (14C)bromodeoxyuridine do label nuclei removed from spinous cells but not from granular cells. CsCl density gradient centrifugation of DNA obtained from early differentiated nuclei which had been exposed in vitro to (14C)bromodeoxyuridine, indicated that a considerable level of the tracer was present in the nucleic acid and suggested that replication of the genome had occurred. Therefore, spinous cells appear to retain the capability of reproducing nuclear DNA. Since differentiated cells appear to have the "diploid" level of DNA, these observations point to the replication of DNA as a possible locus of the mitotic inhibition which is coincident with epidermal differentiation. 相似文献
133.
FL 《中国眼镜科技杂志》2008,(7):77-78
一.管理——摸着石头过河
时下较多的中小企业对于企业管理总有一种摸着石头过河之感.殊不知其实过河的方法很多.摸着石头过河可能是所有方法中最愚蠢的办法.过河其实很简单.你可以借桥过河.寻找相类似而又有成功管理经验的企业搭乘过去.你也可以借船过河.找一些知名的咨询公司设计企业的管理制度。林林总总的过河办法,我看属摸着石头过河最愚蠢。 相似文献
134.
NH Keep FL Norwood CA Moores SJ Winder J Kendrick-Jones 《Canadian Metallurgical Quarterly》1999,285(3):1257-1264
Utrophin is a close homologue of dystrophin, the protein defective in Duchenne muscular dystrophy. Like dystrophin, it is composed of three regions: an N-terminal region that binds actin filaments, a large central region with triple coiled-coil repeats, and a C-terminal region that interacts with components in the dystroglycan protein complex at the plasma membrane. The N-terminal actin-binding region consists of two calponin homology domains and is related to the actin-binding domains of a superfamily of proteins including alpha-actinin, spectrin and fimbrin. Here, we present the 2.0 A structure of the second calponin homology domain of utrophin solved by X-ray crystallography, and compare it to the other calponin homology domains previously determined from spectrin and fimbrin. 相似文献
135.
采用化学改性sol gel提拉法制备Nd(Hsal) 2·hq三元配合物薄膜 ,并对薄膜的性能进行研究 .在薄膜制备中 ,添加适量的表面活性剂可以极大地改善成膜的均匀性和所成膜的表面光洁度 ,且成膜的可重复性很好 .光声光谱研究结果表明 ,Nd3 + 水合离子、Nd2 O3 纳米薄膜中Nd3 + 和Nd(Hsal) 2·hq三元配合物薄膜中Nd3 + 的环境各不相同 ,其超灵敏跃迁峰有较大差别 . 相似文献
136.
The actions of vasopressin and glucagon, administered alone or together, were assessed on bile flow in perfused livers from rats made cholestatic by the injection of ethynylestradiol and from those allowed to recover from such treatment. Concomitant measurements were made of biliary calcium output as well as changes in the perfusate Ca2+ concentration, glucose output, and oxygen uptake. Experiments were also conducted where cholestasis was induced in vitro in the perfused liver by the infusion of phalloidin. In each case cholestasis was demonstrated to have occurred by a reduction in bile flow by approximately 50%. The data show that the transient increase in bile flow and bile calcium seen in control rat liver soon after the administration of vasopressin, particularly when coadministered with glucagon, is largely absent in cholestasis induced by ethynylestradiol and attenuated in cholestasis induced by phalloidin. At the same time the pattern of perfusate Ca2+ fluxes in ethynylestradiol-induced cholestasis shifts to one reflecting net efflux of the ion from the liver. The responses to glucagon administration alone contrast with those of vasopressin in that in the perfused liver of ethynylestradiol-treated rats, glucagon induces a pronounced and sustained increase in bile flow. In cholestasis induced by both ethynylestradiol and phalloidin, glucagon fails to induce an initial transient decrease in bile flow. The effects of glucagon, including enhancement of vasopressin-stimulated bile flow in control and in ethynylestradiol-treated rats, can be mimicked by dibutyryl cyclic adenosine monophosphate (cAMP). Changes in glucose output and oxygen uptake induced by both hormones are only slightly attenuated. The data show that the modulation of bile flow that occurs rapidly after the administration of vasopressin and glucagon to control perfused rat liver is altered in conditions of cholestasis induced by either ethynylestradiol or phalloidin. 相似文献
137.
An independently folding domain of RNA tertiary structure within the Tetrahymena ribozyme 总被引:1,自引:0,他引:1
The Tetrahymena thermophila pre-rRNA contains a 413-nucleotide self-splicing group I intron. This intron has been converted into a sequence-specific endonuclease or ribozyme. A 160-nucleotide portion of the ribozyme consisting of both highly conserved sequence elements (P4 and P6) and nonconserved peripheral extensions (P5abc and P6ab) was synthesized as a separate molecule. Solvent-based Fe(II)-EDTA, a probe that monitors higher-order RNA structure, revealed a protection pattern that was a large subset of that observed in the whole ribozyme. Data from dimethyl sulfate modification and partial digestion with nucleases were also consistent with maintenance of the proper secondary and tertiary structure in the shortened RNA molecule. Thus, this 160-nucleotide molecule (P4-P6 RNA) is an independently folding domain of RNA tertiary structure. A series of mutations and deletions were made within the P4-P6 domain to further dissect its tertiary structure. Fe(II)-EDTA and dimethyl sulfate analysis of these mutants revealed that the domain consists of two substructures, a localized subdomain involving the characteristic adenosine-rich bulge in P5a, and a subdomain-stabilized structure involving long-range interactions. Therefore, like some proteins, the intron RNA is modular, containing a separable domain and subdomain of tertiary structure. 相似文献
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