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61.
The fracture properties of the tempered martensitic steel Eurofer97, which is among the main candidates for fusion power plant structural applications, were studied with two sizes of pre-cracked compact specimens (0.35T C(T) and 0.87T C(T)). The fracture toughness behavior was characterized within the temperature range −80 to −40 °C. The ductile-to-brittle transition reference temperature, as defined in the ASTM standard E1921, was around T0 ≈ −75 °C. At −60 °C, it was found that two sets of toughness data obtained with 0.35T and 0.87T C(T) specimens are not consistent with the size adjustments recommended in the ASTM standard. It was then shown that the underlying reason of this inconsistency is an inappropriate specimen size limit of the ASTM standard for this type of steel. From published fracture toughness data on the tempered martensitic steel F82H steel, similar results were also highlighted. 3D finite elements simulations of the compact specimens were performed to compare the stresses and deformations at the onset of fracture. A local approach model based on the attainment of a critical stress and a critical volume was used to study the constraint loss phenomenon. Within the framework of this model, the strong toughness increase by reducing the specimen size could be satisfactorily explained. 相似文献
62.
Important regulatory factors of intrahepatic protein synthesis and proteolysis are amino acids, glucagon, insulin, and cell volume. We have investigated the changes in these factors with development and after an overnight fast and evaluated their contribution to changes in the hepatic nitrogen balance in vivo. In the fed state, glucagon levels were highest in suckling animals and gradually declined in older rats, whereas the concentration of insulin increased during development. The amino acid concentrations in liver and plasma declined during the suckling period to levels that in vitro are highly permissive for induction of autophagic proteolysis. In all age groups investigated, fasting was associated with a drop in hepatic protein content, together with a marked decrease in hepatocellular volume and insulin concentrations. On the other hand, glucagon concentrations and the concentration of many amino acids in plasma and liver responded to fasting with a pronounced decrease in perinatal and suckling animals, but this response had become blunted at weaning and had disappeared in adult animals. These findings suggest that insulin and/or hepatocellular volume are more likely candidates as short-term physiologic regulators of the hepatic nitrogen balance than are glucagon or amino acids. In glucose-supplemented fetuses, high levels of insulin could not compensate for a decreased hepatocellular volume in averting a catabolic state, suggesting that cell volume is the more important factor. Although our study cannot discriminate between the effects of fasting on protein synthesis and degradation, our findings show unequivocally that, for a rapid growth of the liver, suckling animals have to be fed around-the-clock. 相似文献
63.
S Ottilie PJ Miller DI Johnson CL Creasy MA Sells S Bagrodia SL Forsburg J Chernoff 《Canadian Metallurgical Quarterly》1995,14(23):5908-5919
A STE20/p65pak homolog was isolated from fission yeast by PCR. The pak1+ gene encodes a 72 kDa protein containing a putative p21-binding domain near its amino-terminus and a serine/threonine kinase domain near its carboxyl-terminus. The Pak1 protein autophosphorylates on serine residues and preferentially binds to activated Cdc42p both in vitro and in vivo. This binding is mediated through the p21 binding domain on Pak1p and the effector domain on Cdc42p. Overexpression of an inactive mutant form of pak1 gives rise to cells with markedly abnormal shape with mislocalized actin staining. Pak1 overexpression does not, however, suppress lethality associated with cdc42-null cells or the morphologic defeat caused by overexpression of mutant cdc42 alleles. Gene disruption of pak1+ establishes that, like cdc42+, pak1+ function is required for cell viability. In budding yeast, pak1+ expression restores mating function to STE20-null cells and, in fission yeast, overexpression of an inactive form of Pak inhibits mating. These results indicate that the Pak1 protein is likely to be an effector for Cdc42p or a related GTPase, and suggest that Pak1p is involved in the maintenance of cell polarity and in mating. 相似文献
64.
Interplay between Endothelin and Erythropoietin in Astroglia: The Role in Protection against Hypoxia
Richard Sch?fer Lars Mueller Reinhild Buecheler Barbara Proksch Matthias Schwab Christoph H. Gleiter Lusine Danielyan 《International journal of molecular sciences》2014,15(2):2858-2875
We show that, under in vitro conditions, the vulnerability of astroglia to hypoxia is reflected by alterations in endothelin (ET)-1 release and capacity of erythropoietin (EPO) to regulate ET-1 levels. Exposure of cells to 24 h hypoxia did not induce changes in ET-1 release, while 48–72 h hypoxia resulted in increase of ET-1 release from astrocytes that could be abolished by EPO. The endothelin receptor type A (ETA) antagonist BQ123 increased extracellular levels of ET-1 in human fetal astroglial cell line (SV-FHAS). The survival and proliferation of rat primary astrocytes, neural precursors, and neurons upon hypoxic conditions were increased upon administration of BQ123. Hypoxic injury and aging affected the interaction between the EPO and ET systems. Under hypoxia EPO decreased ET-1 release from astrocytes, while ETA receptor blockade enhanced the expression of EPO mRNA and EPO receptor in culture-aged rat astroglia. The blockade of ETA receptor can increase the availability of ET-1 to the ETB receptor and can potentiate the neuroprotective effects of EPO. Thus, the new therapeutic use of combined administration of EPO and ETA receptor antagonists during hypoxia-associated neurodegenerative disorders of the central nervous system (CNS) can be suggested. 相似文献
65.
Jianqin Zhuang Zhimin Yan Xiumei Liu Xianchun Liu Xiuwen Han Xinhe Bao Ulrich Mueller 《Catalysis Letters》2002,83(1-2):87-91
The acidic properties of TS-1 and Silicalite-1 zeolites have been investigated by the solid-state MAS NMR technique capable of in situ sample pretreatment. As shown by a combination of the 31P MAS NMR and 1H MAS NMR techniques with trimethylphosphine, not only Brønsted acid sites but also Lewis acid sites exist in the TS-1 zeolites. Moreover, TS-1 zeolite is more acidic compared with Silicalite-1. The 1H, 29Si MAS NMR spectra and the resonance related to Brønsted acid species in the 31P MAS NMR spectra demonstrate clearly that the presence of titanium in the framework results in the formation of a new hydroxy group, titanols, which is more acidic than silanols of Silicalite-1. The 31P MAS NMR measurements also illustrate convincingly the existence of at least two different Lewis acid species on the TS-1 zeolites. The conversion of propylene oxide into methoxypropanol catalyzed by TS-1 or Silicalite-1 zeolite in methanol solution as a test reaction has also been described. With the increase of titanium in zeolite, TS-1 appears to have a higher activity during the reaction of propylene oxide to methoxypropanol. 相似文献
66.
Roger Mueller Rainer Jossen Sotiris E. Pratsinis Mark Watson M. Kamal Akhtar 《Journal of the American Ceramic Society》2004,87(2):197-202
Synthesis of zirconia nanoparticles by flame spray pyrolysis (FSP) at high production rates is investigated. Product powder is collected continuously in a baghouse filter unit that is cleaned periodically by air-pressure shocks. Nitrogen adsorption (BET), X-ray diffractometry (XRD), transmission electron microscopy (TEM), and thermogravimetric analysis (TGA) are used to characterize the product powder. The effect of powder production rate (up to 600 g/h), dispersion gas flow rate, and precursor concentration on product particle size, crystallinity, morphology, and purity is investigated. The primary particle size of zirconia is controlled from 6 to 35 nm, while the crystal structure consists of mostly tetragonal phase (80–95 wt%), with the balance monoclinic phase at all process conditions. The tetragonal crystal size is close to the primary particle size, which indicates weak agglomeration of single crystals. 相似文献
67.
Sowdhamini R; Mitchell TJ; Andrew PW; Morgan PJ 《Protein engineering, design & selection : PEDS》1997,10(3):207-215
Pneumolysin and proaerolysin are bacterial toxins that form pores in host
cells by oligomerization. We propose that they may have similar structures
despite a poor sequence identity. The crystal structure of proaerolysin
reveals a protein composed of four domains, arranged in the shape of an
elongated comma. Electron microscopy of the pneumolysin monomer shows a
similar arrangement of domains. The sequence of pneumolysin recognizes the
template of proaerolysin from a library of protein folds. A
three-dimensional model of pneumolysin has been constructed by the
comparative approach using the structure of proaerolysin. This model,
together with results on the activity of site- specific mutants and the
positions of antigenic sites, has been used to propose functional roles of
individual domains.
相似文献
68.
Dr. Florian C. Schrader Dr. Serghei Glinca Dr. Julia M. Sattler Dr. Hans‐Martin Dahse Gustavo A. Afanador Prof. Dr. Sean T. Prigge Prof. Dr. Michael Lanzer Dr. Ann‐Kristin Mueller Prof. Dr. Gerhard Klebe Prof. Dr. Martin Schlitzer 《ChemMedChem》2013,8(3):442-461
Malaria is a potentially fatal disease caused by Plasmodium parasites and poses a major medical risk in large parts of the world. The development of new, affordable antimalarial drugs is of vital importance as there are increasing reports of resistance to the currently available therapeutics. In addition, most of the current drugs used for chemoprophylaxis merely act on parasites already replicating in the blood. At this point, a patient might already be suffering from the symptoms associated with the disease and could additionally be infectious to an Anopheles mosquito. These insects act as a vector, subsequently spreading the disease to other humans. In order to cure not only malaria but prevent transmission as well, a drug must target both the blood‐ and pre‐erythrocytic liver stages of the parasite. P. falciparum (Pf) enoyl acyl carrier protein (ACP) reductase (ENR) is a key enzyme of plasmodial type II fatty acid biosynthesis (FAS II). It has been shown to be essential for liver‐stage development of Plasmodium berghei and is therefore qualified as a target for true causal chemoprophylaxis. Using virtual screening based on two crystal structures of PfENR, we identified a structurally novel class of FAS inhibitors. Subsequent chemical optimization yielded two compounds that are effective against multiple stages of the malaria parasite. These two most promising derivatives were found to inhibit blood‐stage parasite growth with IC50 values of 1.7 and 3.0 μM and lead to a more prominent developmental attenuation of liver‐stage parasites than the gold‐standard drug, primaquine. 相似文献
69.
The trans fatty acid (TFA) patterns in the fats of ruminant meat and dairy products differ from those found in other (processed) fats. We have evaluated different TFA isomers in human breast milk as an indicator of dietary intake of ruminant and dairy fats of different origins. Breast milk samples were collected 1 month postpartum from 310 mothers participating in the KOALA Birth Cohort Study (The Netherlands). The study participants had different lifestyles and consumed different amounts of dairy products. Fatty acid methyl esters were determined by GC-FID and the data were evaluated by principal component analysis (PCA), ANOVA/Post Hoc test and linear regression analysis. The two major principal components were (1) 18:1 trans-isomers and (2) markers of dairy fat including 15:0, 17:0, 11(trans)18:1 and 9(cis),11(trans)18:2 (CLA). Despite similar total TFA values, the 9(trans)18:1/11(trans)18:1-ratio and the 10(trans)18:1/11(trans)18:1-ratio were significantly lower in milk from mothers with high dairy fat intake (40–76 g/day: 0.91 ± 0.48, P < 0.05) compared to low dairy fat intake (0–10 g/day: 1.59 ± 0.48), and lower with strict organic meat and dairy use (>90% organic: 0.92 ± 0.46, P < 0.05) compared to conventional origin of meat and dairy (1.40 ± 0.61). Similar results were obtained for the 10(trans)18:1/11(trans)18:1-ratio. We conclude that both ratios are indicators of different intake of TFA from ruminant and dairy origin relative to other (including industrial) sources. 相似文献
70.
J K Bernard R C Delost F J Mueller J K Miller W M Miller 《Journal of dairy science》1991,74(11):3913-3919
A 22-wk trial was conducted to determine variations in nutrient concentrations of wet and dry corn gluten feed and their effect on nutrient digestibility and milk yield and composition. Holstein cows (n = 48) were blocked at parturition by parity and assigned randomly within block to one of three diets. All cows were fed a control TMR containing corn silage, ground corn, and commercial concentrate plus 2.3 kg/d of alfalfa hay during the 2-wk adjustment period. Thereafter, control diet was fed as wet or dry corn gluten feed substituted for 27% of dietary DM supplied by the control diet. Each cow received TMR for ad libitum consumption. Variations in nutrient concentrations of corn gluten feed were observed throughout the trial. The coefficient of variation was highest for ADIN, and standard deviation was highest for NDF. Intake of CP and NDF and apparent digestibility of DM were greatest when wet or dry corn gluten feed was fed. No differences in DMI, milk yield, and percentages of milk protein, lactose, or SNF were observed, but milk fat percentage was lowest when dry corn gluten feed was fed. Results indicate that corn gluten feed can replace 27% of dietary DM without altering milk yield, but new deliveries should be sampled regularly and amounts fed adjusted to compensate for varying nutrient concentrations. 相似文献