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41.
JK Padia M Field J Hinton K Meecham J Pablo R Pinnock BD Roth L Singh N Suman-Chauhan BK Trivedi L Webdale 《Canadian Metallurgical Quarterly》1998,41(7):1042-1049
We have designed a novel series of CCK-B receptor antagonists by combining key pharmacophores, an arylurea moiety of 1 and a quinazolinone ring of 3, from two known series. Our earlier studies showed that compounds with methylene linkers in our "target" produced moderate binding affinity and selectivity for CCK-B receptors, whereas its higher and lower homologues resulted in loss of affinity. Introduction of -NH- as a linker dramatically enhanced binding affinity and selectivity for CCK-B receptors, thus providing several compounds with single-digit nanomolar binding affinity and excellent selectivity. Analogous to the earlier studies of the series of quinazolinone derivatives 3, we also found 3-isopropoxyphenyl as a preferred substitution on the N-3 quinazolinone. Electron-withdrawing substitutions on the urea terminal phenyl ring enhanced the CCK-B potency. Representative compounds of this series were tested in the functional assay and showed pure antagonist profiles. Compounds 51 and 61 were orally active in the elevated rat X-maze test. These compounds were also evaluated for their pharmacokinetic profile. The absolute oral bioavailability of compound 61 was 22% in rats. 相似文献
42.
This paper deals with the linear elastic analysis of prismatic folded plate and shell structures supported on diaphragms at two opposite edges with the other two edges arbitrarily restrained. The analysis is carried out using curved, variable thickness, Mindlin-Reissner finite strips. The theoretical formulation is presented for a family of C (0) strips and the accuracy and relative performance of the strips are examined for curved situations. Some variable thickness and elastically supported plates are considered and the interesting phenomenon of the occurence of boundary layers in the twisting moments and shear forces is highlighted for a common boundary condition. Other examples analysed include box girders and cylindrical shells. In all cases transverse shear deformation effects are included and the contributions to the strain energy from membrane, bending and transverse shear behaviour noted. In a companion paper these accurate and inexpensive finite strips are used for structural shape optimisation. 相似文献
43.
Cason JA Hinton A Northcutt JK Buhr RJ Ingram KD Smith DP Cox NA 《Journal of food protection》2007,70(9):2056-2062
Broiler chickens from the loading dock of a commercial processing plant were sampled to determine the incidence and counts of coliforms, Escherichia coli, and pathogenic bacteria. Feathers were removed by hand from ten 6-week-old chickens from each of seven different flocks and rinsed in 400 ml of 0.1% peptone water. Heads and feet were removed and rinsed, and the picked carcass was also rinsed, each in 200 ml. The ceca, colon, and crop were aseptically removed and stomached separately in 100 ml of peptone water. Campylobacter was present in six of the seven flocks. Salmonella was isolated from 50 of the 70 carcasses, with at least 2 positive carcasses in each flock, and five-tube most-probable-number (MPN) assays were performed on positive samples. Significantly (P < 0.05) more coliforms and E. coli were found in the ceca than in the feathers, which in turn carried more than the other samples, but total external and internal counts were roughly equivalent. Counts of Campylobacter were higher in the ceca and colon than in the other samples. Salmonella was isolated in external samples from 46 of the 50 positive carcasses compared with 26 positive internal samples or 17 positives in the ceca alone. The total MPN of Salmonella was approximately equivalent in all samples, indicating that contamination was distributed through all external and internal sampling locations. Salmonella-positive samples did not carry higher counts of coliforms or E. coli, and there were no significant correlations between the indicators and pathogens in any sample. Campylobacter numbers in the ceca were correlated with Campylobacter numbers in the feathers and colon, but Salmonella numbers in those samples were not correlated. The pattern of bacterial contamination before processing is complex and highly variable. 相似文献
44.
The benzoxazolinones, specifically benzoxazolin-2(3H)-one (BOA), are important transformation products of the benzoxazinones that can serve as allelochemicals providing resistance
to maize from pathogenic bacteria, fungi, and insects. However, maize pathogens such as Fusarium verticillioides are capable of detoxifying the benzoxazolinones to 2-aminophenol (AP), which is converted to the less toxic N-(2-hydroxyphenyl) malonamic acid (HPMA) and 2-acetamidophenol (HPAA). As biocontrol strategies that utilize a species of
endophytic bacterium, Bacillus mojavensis, are considered efficacious as a control of this Fusarium species, the in vitro transformation and effects of BOA on growth of this bacterium was examined relative to its interaction with strains of F. verticillioides. The results showed that a red pigment was produced and accumulated only on BOA-amended media when wild type and the progeny
of genetic crosses of F. verticillioides are cultured in the presence of the bacterium. The pigment was identified as 2-amino-3H-phenoxazin-3-one (APO), which is a stable product. The results indicate that the bacterium interacts with the fungus preventing
the usual transformation of AP to the nontoxic HPMA, resulting in the accumulation of higher amounts of APO than when the
fungus is cultured alone. APO is highly toxic to F. verticillioides and other organisms. Thus, an enhanced biocontrol is suggested by this in vitro study. 相似文献
45.
We view perceptual tasks such as vision and speech recognition as inference problems where the goal is to estimate the posterior distribution over latent variables (e.g., depth in stereo vision) given the sensory input. The recent flurry of research in independent component analysis exemplifies the importance of inferring the continuous-valued latent variables of input data. The latent variables found by this method are linearly related to the input, but perception requires nonlinear inferences such as classification and depth estimation. In this article, we present a unifying framework for stochastic neural networks with nonlinear latent variables. Nonlinear units are obtained by passing the outputs of linear gaussian units through various nonlinearities. We present a general variational method that maximizes a lower bound on the likelihood of a training set and give results on two visual feature extraction problems. We also show how the variational method can be used for pattern classification and compare the performance of these nonlinear networks with other methods on the problem of handwritten digit recognition. 相似文献
46.
47.
B. R. W. Hinton M. Behrouzvaziri M. Forsyth R. K. Gupta M. Seter P. G. Bushell 《Metallurgical and Materials Transactions A》2012,43(7):2251-2259
A preliminary study showed that the inhibitor lanthanum 4-hydroxy cinnamate ((La4OHcin)3) at a concentration of 400?ppm prevented the hydrogen embrittlement (HE) of SAE 4340 steel tensile specimens when tested under slow strain rate conditions in a 0.01M NaCl. In the presence of the inhibitor, a complex film formed on the surface of specimens during the slow strain rate test (SSRT), and no corrosion pits were detected. Electrochemical polarization studies indicated that the La(4OHcin)3 acted as an anodic inhibitor in the NaCl solution. This article also discusses the mechanism of HE inhibition by La(4OHcin)3. 相似文献
48.
H. Haftchenari F. A. R. Al-Salehi S. T. S. Al-Hassani M. J. Hinton 《Applied Composite Materials》2002,9(2):99-115
A comprehensive study was undertaken to characterise Kevlar reinforced plastic (KRP) angle ply filament wound tubes at different temperatures. Quasi-static burst tests were performed on tubes of 25°, 55° and 75° winding angle. The tubes were burst under internal radial pressure with minimum end constraints. An experimental rig and two conditioning tanks were designed and built to test the specimens at three temperatures; –46°C (low temperature) and +20°C (room temperature) and +70°C (high temperature). For each test the internal pressure and the strains in both circumferential and longitudinal directions were recorded on suitable digital processing equipment.For a particular batch of tubes tested at three different temperatures, an increase in ultimate hoop strain and a decrease in hoop modulus of the 55° tubes with increasing temperatures was recorded; the temperature effect was less pronounced on the corresponding properties of 25° and 75° tubes. The use of a non-structural thin liner during the tests led to a higher ultimate strength of 55° tubes but had negligible effect on the behaviour of 25° and 75° tubes. The 75° tubes failed in a catastrophic fibre fracture under all test conditions. The mode of failure of 55° changed from weeping at 70°C to fibre fracture at –46°C. The 25° tubes failed by weeping with matrix cracking. The matrix cracking was particularly severe when a liner was used. 相似文献
49.
Paige V. Hinton Katelyn J. Genoud James O. Early Fergal J. OBrien Oran D. Kennedy 《International journal of molecular sciences》2022,23(16)
Bone cells, in particular osteoblasts, are capable of communication with each other during bone growth and homeostasis. More recently it has become clear that they also communicate with other cell-types; including chondrocytes in articular cartilage. One way that this process is facilitated is by interstitial fluid movement within the pericellular and extracellular matrices. This stimulus is also an important mechanical signal in skeletal tissues, and is known to generate shear stresses at the micron-scale (known as fluid flow shear stresses (FFSS)). The primary aim of this study was to develop and characterize an in vitro bone–cartilage crosstalk system, to examine the effect of FFSS on these cell types. Specifically, we evaluated the response of osteoblasts and chondrocytes to FFSS and the effect of FFSS-induced soluble factors from the former, on the latter. This system will ultimately be used to help us understand the role of subchondral bone damage in articular cartilage degeneration. We also carried out a comparison of responses between cell lines and primary murine cells in this work. Our findings demonstrate that primary cells produce a more reliable and reproducible response to FFSS. Furthermore we found that at lower magnitudes , direct FFSS produces anabolic responses in both chondrocytes and osteoblasts, whereas higher levels produce more catabolic responses. Finally we show that exposure to osteoblast-derived factors in conditioned media experiments produced similarly catabolic changes in primary chondrocytes. 相似文献
50.