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排序方式: 共有560条查询结果,搜索用时 31 毫秒
1.
Prof. Michael Murray Dr. Ariane Roseblade Dr. Yongjuan Chen Kirsi Bourget Dr. Tristan Rawling 《ChemMedChem》2020,15(2):247-255
Targeting the tumor cell mitochondrion could produce novel anticancer agents. We designed an aryl−urea fatty acid ( 1 g ; 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid) that disrupted the mitochondrion and decreased MDA-MB-231 breast cancer cell viability. To optimize the aryl−ureas the present study evaluated mitochondrial targeting by 1 g analogues containing alkyl chains between 10–17 carbons. Using the dye JC-1, the C12−C17 analogues efficiently disrupted the mitochondrial membrane potential (IC50s 3.5±1.2 to 7.6±1.1 μM) and impaired ATP production; shorter analogues were less active. 7-Aminoactinomycin D/annexin V staining and flow cytometry showed that these agents activated the killing mechanisms of necrosis and apoptosis to varying extents (7-aminoactinomycin D/annexin V staining ratios 4.3–6.0). Indeed, 1 g and its C17 analogue preferentially activated necrosis and apoptosis, respectively (ratios 2.1 and 16). Taken together, alkyl chain length is a determinant of mitochondrial targeting by aryl−ureas and can be varied to develop analogues that activate apoptosis or necrosis in a regulated fashion. 相似文献
2.
E. H. Boutyour H. Zahrouni M. Potier‐Ferry M. Boudi 《International journal for numerical methods in engineering》2004,60(12):1987-2012
The aim of this work is to develop a reliable and fast algorithm to compute bifurcation points and bifurcated branches. It is based upon the asymptotic numerical method (ANM) and Padé approximants. The bifurcation point is detected by analysing the poles of Padé approximants or by evaluating, along the computed solution branch, a bifurcation indicator well adapted to ANM. Several examples are presented to assess the effectiveness of the proposed method, that emanate from buckling problems of thin elastic shells. Especially problems involving large rotations are discussed. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献
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In-plane transport properties of Si/Si1-xGexstructure and its FET performance by computer simulation
Yamada T. Jing-Rong Zhou Miyata H. Ferry D.K. 《Electron Devices, IEEE Transactions on》1994,41(9):1513-1522
Transport properties of ungated Si/Si1-xGex are studied by an ensemble Monte Carlo technique. The device performance is studied with a quantum hydrodynamic equation method using the Monte Carlo results. The phonon-scattering limited mobility is enhanced over bulk Si, and is found to reach 23000 cm2/Vs at 77 K and 4000 cm2/Vs at 300 K. The saturation velocity is increased slightly compared with the bulk value at both temperatures. A significant velocity overshoot, several times larger than the saturation velocity, is also found. In a typical modulation-doped field-effect-transistor, the calculated transconductance for a 0.18 μm gate device is found to be 300 mS/mm at 300 K. Velocity overshoot in the strained Si channel is observed, and is an important contribution to the transconductance. The inclusion of the quantum correction increases the total current by as much as 15% 相似文献
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CV Christodoulou DR Ferry DW Fyfe A Young J Doran TM Sheehan A Eliopoulos K Hale J Baumgart G Sass DJ Kerr 《Canadian Metallurgical Quarterly》1998,16(8):2761-2769
PURPOSE: To determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of a weekly schedule of titanocene dichloride (TD) and to define the pharmacokinetics of titanium in plasma and urine. PATIENTS AND METHODS: Twenty patients with a median age of 58 years received 83 courses of TD. TD was given as 1-hour infusion at escalating doses from 70 to 185 mg/m2/wk. Pharmacokinetic analysis was performed in eight patients for total plasma titanium (TPTi) and in three patients for ultrafiltrable titanium (UFTi). RESULTS: At the fifth dose level (185 mg/m2/wk), a variety of DLTs were seen in five patients: fatigue in three, bilirubinemia in one, and hypokalemia in two. A further six patients were treated at 140 mg/m2; only one had dose-limiting creatinine elevation and this dose was therefore defined as the MTD. No myelosuppression or alopecia were observed. One patient with adenocarcinoma of unknown primary had a minor response. Pharmacokinetic analysis showed that TPTi maximum concentration (Cmax) values were linear with dose and elimination of TPTi was triphasic with a long terminal half-life (t1/2; median, 165 hours; range, 89 to 592). Between 7% and 24.3% of the total of administered titanium was eliminated in urine over the first 24 hours. In contrast, UFTi elimination was described by a one-compartment model with a t1/2 of 0.41 hours; peak levels of UFTi were 5.2% +/- 2.5% those of TPTi. CONCLUSION: The MTD of TD given on a weekly schedule is 140 mg/m2, with cumulative, but reversible creatinine and bilirubin elevation being the DLTs. 相似文献
7.
Andy Gill Tristan Bull Andrew Farmer Garrin Kimmell Ed Komp 《Higher-Order and Symbolic Computation》2012,25(2-4):255-274
In this article we overview the design and implementation of the second generation of Kansas Lava. Driven by the needs and experiences of implementing telemetry decoders and other circuits, we have made a number of improvements to both the external API and the internal representations used. We have retained our dual shallow/deep representation of signals in general, but now have a number of externally visible abstractions for combinatorial and sequential circuits, and enabled signals. We introduce these abstractions, as well as our abstractions for reading and writing memory. Internally, we found the need to represent unknown values inside our circuits, so we made aggressive use of associated type families to lift our values to allow unknowns, in a principled and regular way. We discuss this design decision, how it unfortunately complicates the internals of Kansas Lava, and how we mitigate this complexity. Finally, when connecting Kansas Lava to the real world, the standardized idiom of using named input and output ports is provided by Kansas Lava using a new monad, called Fabric. We present the design of this Fabric monad, and illustrate its use in a small but complete example. 相似文献
8.
Tristan Allard Benjamin Nguyen Philippe Pucheral 《Distributed and Parallel Databases》2014,32(2):191-244
The goal of Privacy-Preserving Data Publishing (PPDP) is to generate a sanitized (i.e. harmless) view of sensitive personal data (e.g. a health survey), to be released to some agencies or simply the public. However, traditional PPDP practices all make the assumption that the process is run on a trusted central server. In this article, we argue that the trust assumption on the central server is far too strong. We propose Met ??P, a generic fully distributed protocol, to execute various forms of PPDP algorithms on an asymmetric architecture composed of low power secure devices and a powerful but untrusted infrastructure. We show that this protocol is both correct and secure against honest-but-curious or malicious adversaries. Finally, we provide an experimental validation showing that this protocol can support PPDP processes scaling up to nation-wide surveys. 相似文献
9.
Linear 1,2-polybutadiene, glass transition temperature (Tg) ?18°C, is crosslinked at ?10°C, to ?20°C by γ irradiation while strained in simple extension, with extension, ratios (λ0) from 1.2 to 2.7. After release, the sample retracts to a state of ease (λs) at room temperature. From equilibrium stress–strain measurements up to a stretch ratio relative to the state of ease (Λ) of 1.2, together with λ0 and λs, the concentration of network strands terminated by trapped entanglements (νN) is calculated. For this purpose, a three-constant Mooney–Rivlin formulation is used, in which the entanglement network is described by Mooney–Rivlin coefficients C1N and C2N, whereas the crosslink networks is described by the coefficient C1x only. The ratio ψN = C2N/(C1N + C2N) is estimated from parallel studies of nonlinear stress relaxation of the uncrosslinked polymer, taking into account the thermal history before and during irradiation. For substantial degrees of crosslinking, i.e., for R0′ = νx/νN > 0.4 (where νN is the concentration of network strands terminated by crosslinks), and for λ0 < 1.8, C2N agrees rather well with the value obtained from stress relaxation of the uncrosslinked polymer in the range of time scale where it is nearly independent of time (1.87 X 105 pascals). The corresponding value of νN is 2.3 × 10?4 moles/cm3, in good agreement with that obtained from viscoelastic measurements of the uncrosslinked polymer in the plateau zone (2.5 × 10?4). However, for R0′ ? 0.2, smaller values of C2N and νN are obtained, indicating that for low degrees of crosslinking the entanglements are not completely trapped. Also, for higher values of λ0, C2N and νN turn out to be somewhat smaller. Similar, less extensive results were obtained previously on a 1,2-polybutadiene with somewhat higher vinyl content and a higher Tg. Crosslinked samples of both these polymers were subjected to equilibrium stress–strain measurements in simple elongation from the state of ease at higher strains up to Λ = 1.7. The results agreed closely with calculations from the three-constant Mooney–Rivlin theory. 相似文献
10.
Tristan Behrens Mehdi Dastani Jürgen Dix Michael Köster Peter Novák 《Annals of Mathematics and Artificial Intelligence》2010,59(3-4):277-311
The Multi-Agent Programming Contest is an annual international event on programming multi-agent systems: Teams of agents participate in a simulated cooperative scenario. It started in 2005 and is organised in 2010 for the sixth time. The contest is an attempt to stimulate research in the area of multi-agent system development and programming by (i) identifying key problems in the field and (ii) collecting suitable benchmarks that can serve as milestones for testing multi-agent programming languages, platforms and tools. This article provides a short history of the contest since it started and reports in more detail on the cows and cowboys scenario implemented for the 2008, 2009 and 2010 contest editions. We briefly discuss the underlying technological background and conclude with a critical discussion of the experiences and lessons learned. 相似文献