全文获取类型
收费全文 | 4780篇 |
免费 | 3篇 |
专业分类
电工技术 | 1篇 |
化学工业 | 18篇 |
能源动力 | 1篇 |
轻工业 | 2篇 |
无线电 | 8篇 |
一般工业技术 | 14篇 |
冶金工业 | 4736篇 |
自动化技术 | 3篇 |
出版年
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 1篇 |
2015年 | 3篇 |
2013年 | 2篇 |
2012年 | 6篇 |
2011年 | 4篇 |
2010年 | 1篇 |
2009年 | 1篇 |
2008年 | 4篇 |
2007年 | 1篇 |
2006年 | 2篇 |
2004年 | 4篇 |
2003年 | 11篇 |
2002年 | 1篇 |
2000年 | 2篇 |
1999年 | 141篇 |
1998年 | 1443篇 |
1997年 | 855篇 |
1996年 | 533篇 |
1995年 | 296篇 |
1994年 | 259篇 |
1993年 | 289篇 |
1992年 | 29篇 |
1991年 | 54篇 |
1990年 | 54篇 |
1989年 | 59篇 |
1988年 | 57篇 |
1987年 | 53篇 |
1986年 | 62篇 |
1985年 | 44篇 |
1983年 | 8篇 |
1982年 | 21篇 |
1981年 | 25篇 |
1980年 | 26篇 |
1979年 | 2篇 |
1978年 | 12篇 |
1977年 | 124篇 |
1976年 | 277篇 |
1975年 | 7篇 |
1962年 | 1篇 |
1955年 | 5篇 |
排序方式: 共有4783条查询结果,搜索用时 15 毫秒
61.
Resistance-modifying agents (RMAs) such as Verapamil have been proved to be effective in reversing multi-drug resistance (MDR) in many in vitro assays. In this study we have investigated the efficacy of Dex-Verapamil, the R-isomer of Verapamil, as a chemosensitizer in a murine leukemia cell line (P388) and in its resistant counterpart (P388/Dx) expressing a typical MDR phenotype. We have examined in vivo the effect of the co-administration of Dex-Verapamil and Doxorubicin in mice transplanted with P388 or P388/Dx cells. Mice treated with the combination of Doxorubicin plus RMA had a significant increase in survival rate as compared to controls; however, the effect was modest. On the contrary, in vitro Dex-Verapamil can enhance Doxorubicin cytotoxicity in P388/Dx cells with a much greater effect depending on the treatment scheme used, by increasing the intracellular content of drug. Taken together our data indicate that Dex-Verapamil can indeed increase the sensitivity to Doxorubicin in resistant cells, but the limited efficacy shown in vivo demonstrates that this phenomenon is strongly dependent on the treatment scheme used and on the maintenance of constantly elevated serum levels. 相似文献
62.
Despite the wider dissemination of health plan report cards, little is known about whether consumers will use this information in making plan and provider choices. Studies of human judgment and decision making are reviewed, as are their implications for devising strategies to inform consumers. The limitations of human information processing suggest that many consumers will not use performance information in making choices. Strategies are needed to support consumers who prefer to rely on intermediaries as well as those who wish to apply the information for their own use. Many current strategies are based on assumptions not supported by existing decision-making research. Although there is much to learn about assisting consumers in making informed choices, a great deal is known from decision-making research. Our approaches and our research agenda must be based on this existing foundation of knowledge. 相似文献
63.
J Seoane K Trinh RM O'Doherty AM Gómez-Foix AJ Lange CB Newgard JJ Guinovart 《Canadian Metallurgical Quarterly》1997,272(43):26972-26977
Glucose-6-phosphatase (G6Pase) catalyzes the hydrolysis of glucose 6-phosphate (Glu-6-P) to free glucose and, as the last step in gluconeogenesis and glycogenolysis in liver, is thought to play an important role in glucose homeostasis. G6Pase activity appears to be conferred by a set of proteins localized to the endoplasmic reticulum, including a glucose-6-phosphate translocase, a G6Pase phosphohydrolase or catalytic subunit, and glucose and inorganic phosphate transporters in the endoplasmic reticulum membrane. In the current study, we used a recombinant adenovirus containing the cDNA encoding the G6Pase catalytic subunit (AdCMV-G6Pase) to evaluate the metabolic impact of overexpression of the enzyme in primary hepatocytes. We found that AdCMV-G6Pase-treated liver cells contain significantly less glycogen and Glu-6-P, but unchanged UDP-glucose levels, relative to control cells. Further, the glycogen synthase activity state was closely correlated with Glu-6-P levels over a wide range of glucose concentrations in both G6Pase-overexpressing and control cells. The reduction in glycogen synthesis in AdCMV-G6Pase-treated hepatocytes is therefore not a function of decreased substrate availability but rather occurs because of the regulatory effects of Glu-6-P on glycogen synthase activity. We also found that AdCMV-G6Pase-treated-cells had significantly lower rates of lactate production and [3-3H]glucose usage, coupled with enhanced rates of gluconeogenesis and Glu-6-P hydrolysis. We conclude that overexpression of the G6Pase catalytic subunit alone is sufficient to activate flux through the G6Pase system in liver cells. Further, hepatocytes treated with AdCMV-G6Pase exhibit a metabolic profile resembling that of liver cells from patients or animals with non-insulin-dependent diabetes mellitus, suggesting that dysregulation of the catalytic subunit of G6Pase could contribute to the etiology of the disease. 相似文献
64.
M Kockx MP de Maat HC Knipscheer JJ Kastelein C Kluft HM Princen T Kooistra 《Canadian Metallurgical Quarterly》1997,78(4):1167-1172
Evaluation of fibrate treatment in humans has focused primarily on its anti-lipidaemic effects. A potentially favourable haemostasis-modulating activity of fibrates has also been recognized but the data are not consistent. We sought to learn more about this variability by examining the effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and fibrinogen in primary hyperlipidaemic patients after six and twelve weeks of treatment using different assay systems for PAI-1 and fibrinogen. Although both fibrates effectively lowered triglyceride and cholesterol levels, no effect on the elevated baseline antigen levels of t-PA and PAI-1 was observed after fibrate treatment. However, both fibrates influenced plasma fibrinogen levels, albeit in a different way. Fibrinogen antigen levels were elevated by 17.6% (p <0.05) and 24.3% (p <0.001) with gemfibrozil after six and twelve weeks, respectively, whereas with ciprofibrate there was no effect. Using a Clauss functional assay with either a mechanical end point or a turbidity-based end point, no significant change in fibrinogen levels was seen after six weeks of gemfibrozil treatment. However, after twelve weeks, gemfibrozil enhanced functional fibrinogen levels by 7.2% (p <0.05) as assessed by the Clauss mechanical assay, but decreased functional fibrinogen levels by 12.5% (p <0.0001) when a Clauss assay based on turbidity was used. After six or twelve weeks of ciprofibrate treatment, functional fibrinogen levels were decreased by 10.1% (p <0.001) and 10.5% (p <0.0001), respectively on the basis of Clauss mechanical and by 14.2% (p <0.001) and 28.2% (p <0.0001), respectively with the Clauss turbidimetric assay. A remarkable and consistent finding with both fibrates was the decrease in functionality of fibrinogen as assessed by the ratio of functional fibrinogen (determined by either of the two Clauss assays) to fibrinogen antigen. Taken together, our results indicate that at least part of the variability in the effects of fibrates on haemostatic parameters can be explained by intrinsic differences between various fibrates, by differences in treatment period and/or by the different outcomes of various assay systems. Interestingly, the two fibrates tested both reduced the functionality of fibrinogen. 相似文献
65.
The humoral immune response of neonates to T cell-independent type 2 (TI-2) Ags is markedly defective. We previously demonstrated that multivalent membrane Ig cross-linking, using dextran-conjugated anti-Ig Abs (anti-Ig-dextran), is an in vitro model for membrane Ig-dependent TI-2 induction of Ig secretion. In this work, we demonstrate that highly purified neonatal B cells are intrinsically defective in IgM secretion in response to anti-Ig-dextran and cytokines in vitro, as well as other modes of B cell activation, relative to adult B cells. However, costimulation of anti-Ig-dextran-activated neonatal B cells with either CD40-ligand, a recombinant bacterial lipoprotein, or LPS restores the IgM secretory response of neonatal B cells to adult levels. Analysis of Ig isotype secretion indicates that neonatal B cells have an enhanced capacity to secrete IgE and IgA relative to other Ig isotypes. These data suggest that neonatal B cells are competent to secrete Ig in response to TI-2 Ags if adequate costimuli are provided, and thus may have particular relevance for the design of vaccine strategies in the immunodeficient host. The data also suggest that neonatal B cells are programmed to secrete relatively enhanced amounts of IgE and IgA, which may be relevant for antimicrobial resistance at mucosal surfaces. 相似文献
66.
WF Shen JC Montgomery S Rozenfeld JJ Moskow HJ Lawrence AM Buchberg C Largman 《Canadian Metallurgical Quarterly》1997,17(11):6448-6458
Recent studies show that Hox homeodomain proteins from paralog groups 1 to 10 gain DNA binding specificity and affinity through cooperative binding with the divergent homeodomain protein Pbx1. However, the AbdB-like Hox proteins from paralogs 11, 12, and 13 do not interact with Pbx1a, raising the possibility of different protein partners. The Meis1 homeobox gene has 44% identity to Pbx within the homeodomain and was identified as a common site of viral integration in myeloid leukemias arising in BXH-2 mice. These integrations result in constitutive activation of Meis1. Furthermore, the Hoxa-9 gene is frequently activated by viral integration in the same BXH-2 leukemias, suggesting a biological synergy between these two distinct classes of homeodomain proteins in causing malignant transformation. We now show that the Hoxa-9 protein physically interacts with Meis1 proteins by forming heterodimeric binding complexes on a DNA target containing a Meis1 site (TGACAG) and an AbdB-like Hox site (TTTTACGAC). Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b, while Hox proteins from other paralogs do not appear to interact with Meis1 proteins. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets. 相似文献
67.
The possible hypocholesterolaemic properties of milk and fermented milk products have been investigated in groups of albino rats given a basal diet, basal diet plus cholesterol, and basal diet plus cholesterol together with whole milk or standard or bifidus yogurt. The yogurts were fortified with skim milk powder, condensed whey or lactose-hydrolysed condensed whey. After 30 d, triacylglycerols, total cholesterol, HDL-cholesterol and LDL-cholesterol were measured in serum. Whole milk and ordinary yogurt had no hypocholesterolaemic effect, but standard yogurt containing lactose-hydrolysed condensed whey and all bifidus yogurts lowered serum cholesterol. In general, yogurts changed HDL-cholesterol little, but tended to raise triacylglycerols. There was marked lowering of LDL-cholesterol in rats given either type of yogurt fortified with whey proteins. This study has demonstrated in a rat model that bifidus yogurts and yogurts fortified with whey proteins can reduce total and LDL-cholesterol, and suggests that if they have the same effect in human subjects they have potential value in cholesterol-lowering diets. 相似文献
68.
Total parenteral nutrition (TPN) is used routinely to maintain patients with the Short Bowel Syndrome (SBS). Until recently, TPN has been the only available therapeutic modality for patients with SBS. Currently, it is the treatment of choice for such individuals and occasionally, when the loss of bowel is extensive, it may be the only way of maintaining life. Unfortunately, TPN is expensive and markedly restrains an individual's lifestyle. Despite the overall success of TPN, the numerous risks associated with its use and the many complications of having an intravenous indwelling for years have served as the stimulus for alternative treatments such as small bowel transplantation (SBT). The first attempts at small bowel transplantation in clinical medicine were by Detterling almost 25 years ago. Patient death or graft loss in these early attempts was caused by the failure to control graft rejection and/or the inability to prevent Graft Versus Host Disease (GVHD). A stimulus for renewed clinical interest in SBT was provided by Starzl et al in 1988 with a report of prolonged graft survival without graft rejection or GVHD in a patient who was the recipient of a multivisceral graft consisting of the entire small bowel and other abdominal organs. Since 1964, 78 Small Bowel transplants have been performed in humans. Several variations of the multivisceral procedure in which the liver and the small bowel constitute the major components of the graft were adopted. The longest survival has been in a child who is still alive with a working graft for more than two years, as reported by Goulet from Paris in 1989. The introduction in SBT of the new immunosuppressive agent FK 506 had provided results which are superior to those achieved with Cyclosporine A (CsA). This latter observation prompted the Pittsburgh group to initiate a large series of isolated and composite intestinal grafts. The remarkable results have demonstrated the clinical utility of intestinal transplantation. This paper will try to summarize the history of the small bowel transplantation until the end of the year 1992, with the current progress in use today. 相似文献
69.
J Arenas MR Gonzalez-Crespo Y Campos MA Martin A Cabello JJ Gomez-Reino 《Canadian Metallurgical Quarterly》1996,39(11):1869-1874
OBJECTIVE: To analyze the levels of free carnitine and carnitine esters in the muscles of patients with inflammatory myopathies. METHODS: Six men and 7 women with inflammatory myopathy and 25 age-matched healthy controls were studied. Free carnitine and carnitine esters in muscle homogenates were measured by a radiochemical procedure. Muscle histochemical staining and measurement of respiratory chain enzyme activity were also performed. RESULTS: Eleven patients had muscle carnitine insufficiency. Five of them had subsarcolemmal oxidative accumulations, 5 had lipid droplets, and 4 had defects of the respiratory chain enzyme complexes. CONCLUSION: Abnormal distribution of muscle carnitine is present in patients with inflammatory myopathies and could impair muscle function. Coexistent mitochondrial dysfunction may contribute to carnitine insufficiency. 相似文献
70.
RS Wallis P Nsubuga C Whalen RD Mugerwa A Okwera D Oette JB Jackson JL Johnson JJ Ellner 《Canadian Metallurgical Quarterly》1996,174(4):727-733
Macrophage activation and tumor necrosis factor-alpha (TNF-alpha) production are critical in tuberculosis immunity but may result in increased human immunodeficiency virus (HIV) expression and accelerated HIV disease progression in HIV-infected persons. Pentoxifylline inhibits expression of TNF-alpha and HIV. A double-blind, placebo-controlled study of adjunctive therapy with pentoxifylline (1800 mg/day) as a timed-release formulation was done in Ugandan HIV-infected patients with pulmonary tuberculosis. Subjects had early HIV disease (mean CD4 cell count, 380/microL) and did not receive other antiretroviral drugs. Pentoxifylline resulted in decreased plasma HIV RNA and serum beta 2-microglobulin and, in a subset of moderately anemic patients, improved blood hemoglobin levels. Trends were noted toward reduced TNF-alpha production in vitro and improved performance scores, but these did not reach statistical significance. No effect was noted on body mass, CD4 cell count, or survival. Additional studies of more potent TNF-alpha inhibitors in HIV-positive subjects with tuberculosis are warranted. 相似文献