全文获取类型
收费全文 | 1539篇 |
免费 | 0篇 |
专业分类
综合类 | 1篇 |
化学工业 | 7篇 |
轻工业 | 13篇 |
一般工业技术 | 2篇 |
冶金工业 | 1511篇 |
自动化技术 | 5篇 |
出版年
2021年 | 1篇 |
2019年 | 2篇 |
2014年 | 1篇 |
2013年 | 3篇 |
2011年 | 1篇 |
2010年 | 5篇 |
2009年 | 1篇 |
2008年 | 1篇 |
2007年 | 3篇 |
2006年 | 2篇 |
2005年 | 1篇 |
2004年 | 1篇 |
2003年 | 3篇 |
1999年 | 40篇 |
1998年 | 479篇 |
1997年 | 259篇 |
1996年 | 179篇 |
1995年 | 83篇 |
1994年 | 74篇 |
1993年 | 90篇 |
1992年 | 11篇 |
1991年 | 10篇 |
1990年 | 20篇 |
1989年 | 13篇 |
1988年 | 15篇 |
1987年 | 11篇 |
1986年 | 14篇 |
1985年 | 15篇 |
1982年 | 4篇 |
1981年 | 10篇 |
1980年 | 20篇 |
1979年 | 1篇 |
1978年 | 7篇 |
1977年 | 50篇 |
1976年 | 99篇 |
1975年 | 5篇 |
1964年 | 2篇 |
1955年 | 2篇 |
1954年 | 1篇 |
排序方式: 共有1539条查询结果,搜索用时 0 毫秒
51.
Benztropine and its analogs are tropane ring-containing dopamine uptake inhibitors that produce behavioral effects markedly different from cocaine and other dopamine transporter blockers. We investigated the benztropine binding site on dopamine transporters by covalently attaching a benztropine-based photoaffinity ligand, [125I]N-[n-butyl-4-(4"'-azido-3"'-iodophenyl)]-4', 4"-difluoro-3alpha-(diphenylmethoxy)tropane ([125I]GA II 34), to the protein, followed by proteolytic and immunological peptide mapping. The maps were compared with those obtained for dopamine transporters photoaffinity labeled with a GBR 12935 analog, [125I]1-[2-(diphenylmethoxy)ethyl]-4-[2-(4-azido-3-iodophenyl)ethy l]p iperazine ([125I]DEEP), and a cocaine analog, [125I]3beta-(p-chlorophenyl)tropane-2beta-carboxylic acid, 4'-azido-3'-iodophenylethyl ester ([125I]RTI 82), which have been shown previously to interact with different regions of the primary sequence of the protein. [125I]GA II 34 became incorporated in a membrane-bound, 14 kDa fragment predicted to contain transmembrane domains 1 and 2. This is the same region of the protein that binds [125I]DEEP, whereas the binding site for [125I]RTI 82 occurs closer to the C terminal in a domain containing transmembrane helices 4-7. Thus, although benztropine and cocaine both contain tropane rings, their binding sites are distinct, suggesting that dopamine transport inhibition may occur by different mechanisms. These results support previously derived structure-activity relationships suggesting that benztropine and cocaine analogs bind to different domains on the dopamine transporter. These differing molecular interactions may lead to the distinctive behavioral profiles of these compounds in animal models of drug abuse and indicate promise for the development of benztropine-based molecules for cocaine substitution therapies. 相似文献
52.
This paper presents a full reconstruction process of magnetic resonance images. The first step is to bring the acquired data from the frequency domain, using a Fast Fourier Transform algorithm. A Tomographic Image Interpolation is then used to transform a sequence of tomographic slices in an isotropic volume data set, a process also called 3D Reconstruction. This work describes an automatic method whose interpolation stage is based on a previous matching stage using Delaunay Triangulation. The reconstruction approach uses an extrapolation procedure that permits appropriate treatment of the boundaries of the object under analysis. 相似文献
53.
54.
The five- to six-year all-cause mortality is analysed in 1323 newly diagnosed diabetic patients aged 40 years or over. The median age at diagnosis is lower for males (63.6 years) than for females (67.5 years), but more males (24.7%) than females (20.0%) have died (p = 0.04). This male excess mortality can mainly be attributed to the 60-79-year old males. With increasing diabetes duration both male and female diabetic patients exhibit an increasing excess mortality in comparison with the Danish population. For males this excess mortality becomes statistically significant four years after diagnosis for the 40-59 year-olds and after six years for the 60-79 year-olds. For females and very old males no statistically significant excess mortality is observed, but after two to four years there is a tendency for the survival curve of 40-79-year old females to separate from that of the Danish female population to show an excess mortality. In this population-based study the disadvantageous mortality experience of even newly-diagnosed diabetic patients is clearly demonstrated. 相似文献
55.
Trypanothione reductase (TR), a flavoprotein oxidoreductase central to the unique thiol-redox system that operates in trypanosomatid protozoa, has been proposed as a potential target for the chemotherapy of trypanosomatid infections. In this study, targeted gene replacement was used to obtain evidence that TR is an essential cellular component and that its physiological function is crucial for parasite survival. Precise replacement of the Leishmania donovani tryA gene encoding TR was only possible upon simultaneous expression of the tryA coding region from an episome; in its absence, attempted removal of the last tryA allele invariably led to the generation of an extra copy of tryA, seemingly as a result of selective chromosomal polysomy. Partial replacement mutants were drastically affected in their ability to survive inside cytokine-activated macrophages in a murine model of Leishmania infection. As no compensatory mechanism for the partial loss of TR activity was observed in these mutants and as it was not possible to obtain viable Leishmania devoid of TR catalytic activity, specific inhibitors of this enzyme are likely to be useful anti-leishmanial agents for chemotherapeutic use. 相似文献
56.
SH Willis AH Rux C Peng JC Whitbeck AV Nicola H Lou W Hou L Salvador RJ Eisenberg GH Cohen 《Canadian Metallurgical Quarterly》1998,72(7):5937-5947
Previously, we showed that truncated soluble forms of herpes simplex virus (HSV) glycoprotein D (gDt) bound directly to a truncated soluble form of the herpesvirus entry mediator (HveAt, formerly HVEMt), a cellular receptor for HSV. The purpose of the present study was to determine the affinity of gDt for HveAt by surface plasmon resonance and to compare and contrast the kinetics of an expanded panel of gDt variants in binding to HveAt in an effort to better understand the mechanism of receptor binding and virus entry. Both HveAt and gDt are dimers in solution and interact with a 2:1 stoichiometry. With HveAt, gD1(306t) (from the KOS strain of HSV-1) had a dissociation constant (KD) of 3.2 x 10(-6) M and gD2(306t) had a KD of 1.5 x 10(-6) M. The interaction between gDt and HveAt fits a 1:1 Langmuir binding model, i.e., two dimers of HveAt may act as one binding unit to interact with one dimer of gDt as the second binding unit. A gD variant lacking all signals for N-linked oligosaccharides had an affinity for HveAt similar to that of gD1(306t). A variant lacking the bond from cysteine 1 to cysteine 5 had an affinity for HveAt that did not differ from that of the wild type. However, variants with double cysteine mutations that eliminated either of the other two disulfide bonds showed decreased affinity for HveAt. This result suggests that two of the three disulfide bonds of gD are important for receptor binding. Four nonfunctional gDt variants, each representing one functional domain of gD, were also studied. Mutations in functional regions I and II drastically decreased the affinity of gDt for HveAt. Surprisingly, a variant with an insertion in functional region III had a wild-type level of affinity for HveAt, suggesting that this domain may function in virus entry at a step other than receptor binding. A variant with a deletion in functional region IV [gD1(Delta290-299t)] exhibited a 100-fold enhancement in affinity for HveAt (KD = 3.3 x 10(-8) M) due mainly to a 40-fold increase in its kinetic on rate. This agrees with the results of other studies showing the enhanced ability of gD1(Delta290-299t) to block infection. Interestingly, all the variants with decreased affinities for HveAt exhibited decreased kinetic on rates but only minor changes in their kinetic off rates. The results suggest that once the complex between gDt and HveAt forms, its stability is unaffected by a variety of changes in gD. 相似文献
57.
The triumph of antibiotics over bacterial pathogens that has occurred in the latter half of this century looks increasingly threatened as we approach the new millennium. Increasing resistance in important pathogens such as Mycobacterium tuberculosis, Shigella, and Streptococcus pneumoniae threatens the lives of millions. The increasing problems with drug resistance in (C. diphtheriae, Salmonella typhi and the pneumococcus in Vietnam are presented as examples of the challenge confronting tropical countries. 相似文献
58.
TJ De Vries AN Schoffelmeer R Binnekade AH Mulder LJ Vanderschuren 《Canadian Metallurgical Quarterly》1998,10(11):3565-3571
The present study was designed to evaluate the relationship between reinstatement of drug-seeking behaviour following long-term extinction of intravenous (i.v.) drug self-administration (an animal model for craving) and long-term behavioural sensitization. Rats were allowed to self-administer heroin (50 microg/kg per inj., 14 daily sessions), cocaine (500 microg/kg per inj., 10 daily sessions) or saline. Following a 3-week extinction period, reinstatement tests were performed to evaluate priming effects of amphetamine, cocaine and heroin on nonreinforced drug-seeking behaviour. In addition, the occurrence of long-term behavioural sensitization in rats with a history of heroin or cocaine self-administration was determined. Heroin-seeking behaviour was reinstated by heroin (0.25 mg/kg), amphetamine (1.0 mg/kg) and cocaine (10 mg/kg). In addition, animals with a history of heroin self-administration displayed locomotor sensitization to both heroin and amphetamine. Cocaine-seeking behaviour was reinstated by cocaine and amphetamine, but not by heroin. Interestingly, locomotor sensitization to amphetamine, but not heroin, was observed in animals with a history of cocaine self-administration. In other words, the induction of drug-seeking behaviour following a prolonged drug-free period was found to be associated with the expression of long-term behavioural sensitization. These data provide experimental evidence for a role of behavioural sensitization in the incentive motivation underlying drug-seeking behaviour. If drug hyperresponsiveness would indeed be a crucial factor in drug-induced craving in human addicts, pharmacological readjustment of the neuroadaptations underlying drug sensitization may prevent relapse to drug use long after detoxification. 相似文献
59.
60.
RA Memon WM Holleran AH Moser T Seki Y Uchida J Fuller JK Shigenaga C Grunfeld KR Feingold 《Canadian Metallurgical Quarterly》1998,18(8):1257-1265
Alterations in triglyceride and cholesterol metabolism often accompany inflammatory diseases and infections. We studied the effects of endotoxin (lipopolysaccharide [LPS]) and cytokines on hepatic sphingolipid synthesis, activity of serine palmitoyltransferase (SPT), the first and rate-limiting enzyme in sphingolipid synthesis, and lipoprotein sphingolipid content in Syrian hamsters. Administration of LPS induced a 2-fold increase in hepatic SPT activity. The increase in activity first occurred at 16 hours, peaked at 24 hours, and was sustained for at least 48 hours. Low doses of LPS produced maximal increases in SPT activity, with half-maximal effect seen at approximately 0.3 microg LPS/100 g body weight. LPS increased hepatic SPT mRNA levels 2-fold, suggesting that the increase in SPT activity was due to an increase in SPT mRNA. LPS treatment also produced 75% and 2.5-fold increases in hepatic sphingomyelin and ceramide synthesis, respectively. Many of the metabolic effects of LPS are mediated by cytokines. Interleukin 1 (IL-1), but not tumor necrosis factor, increased both SPT activity and mRNA levels in the liver of intact animals, whereas both IL-1 and tumor necrosis factor increased SPT mRNA levels in HepG2 cells. IL- produced a 3-fold increase in SPT mRNA in HepG2 cells, and the half-maximal dose was 2 ng/mL. IL-1 also increased the secretion of sphingolipids into the medium. Analysis of serum lipoprotein fractions demonstrated that very low density lipoprotein, intermediate density lipoprotein, and low density lipoprotein isolated from animals treated with LPS contained significantly higher amounts of ceramide, glucosylceramide, and sphingomyelin. Taken together, these results indicate that LPS and cytokines stimulate hepatic sphingolipid synthesis, which results in an altered structure of circulating lipoproteins and may promote atherogenesis. 相似文献