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131.
Mechanisms mediating the inheritance of mitochondria are poorly understood, but recent studies with the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe have begun to identify components that facilitate this essential process. These components have been identified through the analysis of conditional yeast mutants that display aberrant mitochondrial distribution at restrictive conditions. The analysis of these mutants has uncovered several novel proteins that are localized either to cytoskeletal structures or to the mitochondria themselves. Many mitochondrial inheritance mutants also show altered mitochondrial morphology and defects in maintenance of the mitochondrial genome. Although some inheritance components and mechanisms appear to function specifically in certain types of cells, other conserved proteins are likely to mediate mitochondrial behavior in all eukaryotic cells. 相似文献
132.
TJ Yoon YC Yoo TB Kang YJ Baek CS Huh SK Song KH Lee I Azuma JB Kim 《Canadian Metallurgical Quarterly》1998,20(4-5):163-172
We here demonstrated the prophylactic effect of an extract (KM-110) from Viscum album coloratum, a Korean mistletoe, on tumor metastasis produced by highly metastatic tumor cells, colon 26-M3.1 carcinoma, B16-BL6 melanoma and L5178Y-ML25 lymphoma cells, using experimental models in mice. Intravenous (i.v.) administration of KM-110 (100 microg/mouse) 2 days before tumor inoculation significantly inhibited lung metastasis of B16-BL6 and colon 26-M3.1 cells, and liver and spleen metastasis of L5178Y-ML25 cells. The prophylactic effect of KM-110 on tumor metastasis was evident with various administration routes, i.e. subcutaneous, oral, intranasal as well as i.v., and was dependent upon the dose of KM-110 administered. Furthermore, mice given KM-110 (100 microg) 2 days before tumor inoculation showed significantly prolonged survival rates compared with the untreated mice. In a time course analysis of NK activity, i.v. administration of KM-110 (100 microg) significantly augmented NK cytotoxicity to Yac-a tumor cells from 1 to 3 days after KM-110 treatment. Furthermore, depletion NK cells by injection of rabbit anti-asialo GM1 serum completely abolished the inhibitory effect of KM-110 on lung metastasis of colon 26-M3.1 cells. These results suggest that KM-110 possesses immunopotentiating activity which enhances the host defense system against tumors, and that its prophylactic effect on tumor metastasis is mediated by NK cell activation. 相似文献
133.
DR Smith PJ Fedorka-Cray R Mohan KV Brock TE Wittum PS Morley KH Hoblet LJ Saif 《Canadian Metallurgical Quarterly》1998,59(8):986-993
OBJECTIVE: To identify exposures to etiologic agents and to identify characteristics that could explain risk of disease for adult cattle in herds affected by winter dysentery (WD). ANIMALS: 229 lactating and nonlactating adult cattle (125 case and 104 control cattle) selected from 12 dairy herds. PROCEDURE: A case-control study, using multivariate conditional logistic regression and controlling for herd effects, was used to develop a model for risk factors associated with disease for each cow. RESULTS: Likelihood of developing disease increased as the ELISA value for bovine coronavirus (BCV) antigen detectable in feces increased (odds ratio [OR] = 2.94 for each 0.100 increase in BCV antigen ELISA value). Pregnant cattle were less likely to develop WD, compared with nonpregnant herdmates. Cows with high acute BCV antibody titers that seroresponded had greater odds of developing disease, compared with seroresponding cows with low acute titers. However, among those cows that did not serorespond, high acute antibody titers were associated with lower odds of developing the disease. CONCLUSION: In herds affected by WD, ill cows were more likely to shed detectable amounts of BCV antigen in their feces, and pregnancy appeared to protect cattle from the disease. The measured interaction between BCV seroresponse and acute BCV antibody titer may be evidence of an immunopathologic condition, but could also have been attributable to dynamics of the ELISA or study design. CLINICAL RELEVANCE: Factors that explained a cow's risk for illness within WD-affected herds may have been surrogate measures for that cow's nonspecific and BCV-specific immune profile. 相似文献
134.
KH Kilburn 《Canadian Metallurgical Quarterly》1996,38(10):1018-1025
A container truck leaked 800 L (200 gallons) of hydrochloric acid (HCl) near a mobile home park in Louisiana in August 1993. The investigating officer and residents became acutely ill with burning and tearing eyes, burning throats, headache, chest pain, shortness of breath, and flu-like complaints. Twenty months later, 45 exposed adult subjects and 56 age-matched referents underwent neurobehavioral testing, including balance, reaction time, blink-reflex latency, and spirometry. They also completed health questionnaires and a profile of mood states. The exposed subjects differed significantly from referents by t test and by covariance analysis for balance, simple and two-choice visual reaction time, digit symbol, and for placing pegs in a pegboard. Proximity to the HCl spill increased sway speeds and impaired pulmonary midflow rates. Chronic neurobehavioral dysfunction and airways obstruction were found after environmental HCl exposure. 相似文献
135.
Inspiratory muscle function has been shown to be related to general muscle weakness, weight loss, blood gas tensions, airway obstruction and hyperinflation. The aim of this study was to define (1) the factor that is the main determinant of the tension-time index of the inspiratory muscles (TTmus), and which this increases the risk of inspiratory muscle fatigue; and (2) whether a breathing strategy is adopted to avoid inspiratory muscle fatigue. Twenty-seven normal volunteers and 35 stable COPD outpatients (FEV1% predicted, range: 21-89%; and FRC/TLC, range: 49-77%) were studied. The TTmus was determined as follows: TTmus = PI/PImax.TI/Ttot, where Pi is the mean inspiratory pressure calculated from the mouth occlusion pressure (P0.1), PImax is the maximal inspiratory pressure, TI is the inspiratory time, and Ttot is the total time of the breathing cycle. COPD patients showed significantly lower PImax and higher P0.1, PI, PI/PImax, and TTmus than normal subjects. No patient had a TTmus value higher than the inspiratory muscle fatigue threshold of 0.33. The FEV1 was significantly correlated with TTmus and all its components in the patients. The FRC/TLC was also correlated with all components except PI. Body weight was only correlated with PImax. In a forward and backward stepwise regression analysis, FEV1 appeared to be the only significant factor explaining the variance of log (PI/PImax) and log (TTmus), whereas FRC/TLC was the principal determinant of PImax. In COPD patients, a non-linear relationship was found between TI and P0.1. A negative linear relationship was found between TI/Ttot and PI/PImax. In conclusion, although hyperinflation predominantly affected inspiratory muscle strength in a group of stable COPD patients with a wide range of severity, airway obstruction was the principal factor determining the magnitude of TTmus. In addition, in order to remain below the inspiratory muscle fatigue threshold, as the severity of airway obstruction increased, patients adopted a breathing strategy characterized by decreased TI/Ttot as inspiratory pressure demand increased. 相似文献
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139.
M Peters P Schirmacher J Goldschmitt M Odenthal C Peschel E Fattori G Ciliberto HP Dienes KH Meyer zum Büschenfelde S Rose-John 《Canadian Metallurgical Quarterly》1997,185(4):755-766
Soluble cytokine receptors modulate the activity of their cognate ligands. Interleukin (IL)-6 in association with the soluble IL-6 receptor (sIL-6R) can activate cells expressing the gp130 signal transducer lacking the specific IL-6R. To investigate the function of the IL-6-sIL-6R complex in vivo and to discriminate the function of the IL-6-sIL-6R complex from the function of IL-6 alone, we have established a transgenic mouse model. Double-transgenic mice coexpressing IL-6 and sIL-6R were generated and compared with IL-6 and sIL-6R single-transgenic mice. The main phenotype found in IL-6-sIL-6R mice was a dramatic increase of extramedullary hematopoietic progenitor cells in liver and spleen but not in the bone marrow. In IL-6 single-transgenic mice and sIL-6R single-transgenic mice no such effects were observed. The high numbers of hematopoietic progenitor cells were reflected by a strong increase of peripheral blood cell numbers. Therefore, activators of the gp130 signal transducer like the IL-6-IL-6R complex may represent most powerful stimulators for extramedullary hematopoietic progenitor cells. gp130 activators may become important for the expansion of hematopoietic progenitor cells in vivo and in vitro. 相似文献
140.
BACKGROUND: Invasive growth of epithelial tumor cells, a major cause of death from cancer in humans, involves loss of epithelial polarity and dedifferentiation. Transforming growth factor beta (TGFbeta) is regarded as a major tumor suppressor during early tumor development because it inhibits cell-cycle progression and tumor growth. Many dedifferentiated, late-stage tumors are resistant to growth inhibition by TGFbeta, however, and even secrete TGFbeta. In line with this, TGFbeta is involved in angiogenesis, wound healing and epithelial-mesenchymal transition (EMT) during development. Ha-Ras-transformed mammary epithelial cells (EpRas) undergo TGFbeta-induced EMT maintained via a TGFbeta autocrine loop. Thus, we have analyzed whether signal transduction by the TGFbeta receptor (TGFbetaR) is required for local tumor cell invasion and metastasis. RESULTS: A dominant-negative type II TGFbetaR (TGFbetaRII-dn) was expressed using retroviral vectors in EpRas cells and highly metastatic mesenchymal mouse colon carcinoma cells (CT26). In both cell types, TGFbetaRII-dn blocked TGFbetaR signaling and heavily delayed tumor formation. In EpRas cells, TGFbetaRII-dn prevented EMT. In the dedifferentiated mesenchymal CT26 cells, TGFbetaRII-dn caused mesenchymal-to-epithelial transition and inhibited their in vitro invasiveness in several assays. In addition, TGFbetaRII-dn completely abolished metastasis formation by CT26 cells. Furthermore, several human carcinoma lines lost in vitro invasiveness when treated with neutralizing TGFbeta antibodies or soluble receptor variants. Finally, human colon carcinoma cells (hnPCC) expressing a mutated, non-functional TGFbetaRII were non-invasive in vitro, a defect restored by re-expressing wild-type TGFbetaRII. CONCLUSIONS: Cell-autonomous TGFbeta signaling is required for both induction and maintenance of in vitro invasiveness and metastasis during late-stage tumorigenesis. TGFbetaRII therefore represents a potential target for therapeutical intervention in human tumorigenesis. 相似文献