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VA Tyurin YY Tyurina PJ Quinn NF Schor R Balachandran BW Day VE Kagan 《Canadian Metallurgical Quarterly》1998,60(2):270-281
Incubation of mock-transfected PC12 rat pheochromocytoma cells (PC12) for 2 h with increasing concentrations of glutamate caused progressive loss of viability (e.g., 67% with 15 mM glutamate). In contrast, the viability of bcl-2-transfected cells (PC12/bcl-2) was unaffected by glutamate. Neither PC12 nor PC12/bcl-2 cells showed a significant incidence of apoptosis in response to glutamate. Conventional phospholipid analysis by high-performance TLC and phosphorous determination showed no significant changes in the phospholipid composition of either cell line incubated with =15 mM glutamate. Phospholipid peroxidation was quantified in the cells using our newly developed method based on fluorescence-HPLC analysis of metabolically incorporated oxidation-sensitive and fluorescent fatty acid, cis-parinaric acid. Unlike previous studies that measured total phospholipid oxidation, this novel technology permitted quantitation of oxidative stress in different classes of labeled phospholipids (the amount of labeled phospholipids in the cells did not exceed 1% of total phospholipids). Significant peroxidation of phosphatidylcholine and phosphatidylethanolamine occurred in PC12 cells treated with >5 mM glutamate. The peroxyl radical initiator 2,2'-azobis(2,4-dimethylvaleronitrile) caused a pronounced loss of all major phospholipid classes in PC12 cells, but no loss of cell viability. No phospholipid peroxidation was detected in PC12/bcl-2 cells incubated with =15 mM glutamate or with 2, 2'-azobis(2,4-dimethylvaleronitrile). These results directly demonstrate that peroxidation of membrane phospholipids is not responsible for the cytotoxicity of glutamate in PC12 cells. Total cellular thiol, protein thiol and GSH reserves were quantified by a previously described electron paramagnetic resonance spectrometric method. Total thiols were ca. 1.5-fold greater in PC12/bcl-2 than in PC12 cells. Glutamate (=5 mM) caused a progressive and equally significant decrease in total thiols and GSH in both PC12 and PC12/bcl-2 cells. High glutamate concentrations caused oxidation of protein sulfhydryls in PC12 cells, but not in PC12/bcl-2 cells. The results suggest that the changes in cellular milieu caused by bcl-2 gene transfection protect PC12 cells from the toxic effects of glutamate in a manner consistent with prevention of protein sulfhydryl oxidation. 相似文献
34.
Prevention by nerve growth factor (NGF) of apoptotic death in neural cells has been variously ascribed to binding of NGF to its low-affinity (p75) or high-affinity (trkA) receptor or to a cooperative interaction between the two. In a series of studies using, in turn, neuroblastoma cell lines that express only p75, mutant NGF species that bind selectively to either p75 or trkA, and a polyclonal antibody that binds to the NGF-binding domain of p75, we demonstrate that NGF binding to p75 is both necessary and sufficient for the abrogation of apoptosis in neuroblastoma cells treated with antimitotic agents. 相似文献
35.
KS Ternovo? TN Selezneva AV Akleev IA Pashkov LA Noskin NV Klopov VA Noskin NF Starodub 《Canadian Metallurgical Quarterly》1998,70(3):81-85
The effects of an alternative chelation program in thalassemic patients with severe iron overload are investigated. The schedule of treatment, feasible at home, consists in the administration of deferoxamine intravenously (100 mg/kg/die 8 hours 10 days a month), followed by 50 mg/kg/die subcutaneously in the remaining 20 days of the month. The results in 34 patients who underwent this program over 8 months are reported. After intensive chelation therapy serum ferritin and transaminase levels were significantly lower, and daily urinary iron excretion values were significantly higher when compared to the levels observed before the treatment. After the period of study, echocardiography revealed an ejection fraction (EF) significantly higher in 15 out of 34 cardiopathic patients. In conclusion, the alternative chelation program is effective in reducing iron overload of thalassemic patients, protecting them also against cardiac disease. 相似文献
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In this review a case is presented for the use of mathematical modelling in the study of pain. The philosophy of mathematical modelling is outlined and a recommendation is made for the use of modern nonlinear techniques and computational neuroscience in the modelling of pain. Classic and more recent examples of modelling in neurobiology in general and pain in particular, at three different levels-molecular, cellular and neural networks-are described and evaluated. Directions for further progress are indicated, particularly in plasticity and in modelling brain mechanisms. Major advantages of mathematical modelling are that it can handle extremely complex theories and it is non-invasive, and so is particularly valuable in the investigation of chronic pain. 相似文献
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T Gross K Richert C Mierke M Lützelberger NF K?ufer 《Canadian Metallurgical Quarterly》1998,26(2):505-511
Smad6 and Smad7 function as intracellular antagonists in transforming growth factor-beta (TGF-beta) signaling. Here we report the isolation of human Smad6, which is closely related to Smad7. Smad6 and Smad7 mRNAs were differentially expressed in lung cancer cell lines and were rapidly and directly induced by TGF-beta1, activin and bone morphogenetic protein-7. Cross-talk between TGF-beta and other signaling pathways was demonstrated by the finding that epidermal growth factor (EGF) induced the expression of inhibitory SMAD mRNA. Moreover, whereas the phorbol ester PMA alone had no effect, it potentiated the TGF-beta1-induced expression of Smad7 mRNA. Ectopic expression of anti-sense Smad7 RNA was found to increase the effect of TGF-beta1, supporting its role as a negative regulator in TGF-beta signaling. Thus, expression of inhibitory Smads is induced by multiple stimuli, including the various TGF-beta family members, whose action they antagonize. 相似文献
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VK Mazurik VF Mikha?lov LN Ushenkova NA Vodolazskaia NF Raeva GA Chernov TG Shliakova MV Borovkov 《Canadian Metallurgical Quarterly》1997,37(2):165-174
The DNA and RNA contents, RNA/DNA ratio, and spontaneous and latex-induced oxidant activity indices of the whole blood were studied in the nitroblue tetrazolium test of mono- and polymorphonuclear blood leucocytes of intact dogs after injection of lipopolysaccharide pyrogenal. Significant changes in the above parameters were revealed for radioresistant (survived) and radiosensitive (lost) animals exposed to a subsequent prolonged gamma irradiation with a lethal dose of 7.64 Gy (LD75/45). Peroral introduction of 30 mg/kg indometofen (an indole analog of tamoxifen), which is a potential radioprotector, to dogs increased the survival rates of the irradiated dogs up to 93% and aided in the adaptive biochemical changes in the nuclear cell compartment of blood to induce a radioresistant status of the organism. 相似文献