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91.
OBJECTIVE: To determine whether adaptive cytoprotection exists in human intestinal cells under in vitro conditions and what role, if any, endogenous prostaglandins or calcium may play in mediating this protective response. SUMMARY BACKGROUND DATA: Adaptive cytoprotection can be defined as that process whereby the administration of a low concentration of a damaging agent, termed a "mild irritant," which by itself is not injurious, can attenuate gastrointestinal mucosal injury subsequently induced by the application of higher concentrations of the same or other necrotizing agents. Despite substantial investigation, the mediator or mediators of adaptive cytoprotection remain poorly understood. METHODS: Postconfluent Caco-2 cells were used in all experiments. Cellular death was quantitated using a dual-component fluorescent assay. Changes in intracellular calcium concentration were quantitated by measuring fluorescent signal changes of the single wavelength calcium indicator (Fluo-3). Finally, prostaglandin E2 release into the media was quantitated by radioimmunoassay. RESULTS: Pretreatment of Caco-2 cells with low concentrations of ethanol (mild irritant) significantly attenuated injury induced by higher damaging concentrations of ethanol. The protection conferred by the mild irritant was directly dependent on both the concentration of the irritant used and the duration of exposure and was abrogated when cells were pretreated with an endogenous prostaglandin inhibitor (indomethacin) or if the mild irritant was administered in calcium-free media. Cells exposed to ethanol had a significant and concentration-dependent increase in intracellular calcium concentration, an effect that was highly related to cellular injury. Pretreatment with a mild irritant significantly decreased intracellular calcium increases induced by not only ethanol but also by a calcium ionophore (A23187). Cells treated with low concentrations of ethanol demonstrated no significant elevation in prostaglandin E2 release. CONCLUSIONS: Adaptive cytoprotection induced by ethanol exists in human colonocytes under in vitro conditions independent of mucosal blood flow, neural innervation, or circulating humoral factors. The authors' data suggest that this response does not require endogenous prostaglandin synthesis but may involve processes whereby intracellular calcium accumulation is prevented.  相似文献   
92.
One significant characteristic of the airway mucosa in vivo, that cannot easily be mimicked in vitro, is its microcirculation, which generates a highly dynamic, biologically active milieu of plasma-derived molecules that may pass to the airway lumen in vivo. New data on the mechanisms of airway mucosal exudation indicate that the protein systems of circulating plasma may contribute significantly to the biology and immunology of the lamina propria, its surface epithelium and the luminal surface, not only in injured airways, but also in airways that are activated but display no sign of oedema, epithelial disruption, or increased absorption capacity. We suggest that present knowledge of the mechanisms of plasma exudation, together with rapidly emerging information (not detailed herein) on receptors, target cells and cellular responses to the plasma-derived molecules, must be considered in any realistic model that investigates "immuno-inflammatory" mechanisms of the airway mucosa.  相似文献   
93.
Mild, severe, and dyssocial subtypes of alcohol dependence, previously identified among Caucasian men from the Epidemiologic Catchment Area study, were also identified among Caucasian men and women with DSM-IV alcohol dependence from the National Longitudinal Alcohol Epidemiologic Survey (n = 2,703; 1,746 respectively). These subtypes were not identified among African American and Hispanic American men or women with DSM-IV alcohol dependence. Among Caucasians with alcohol dependence, the subtypes were characterized by differential loading on three dimensions: genetic, general environmental, and dyssocial environmental symptom scales developed in a prior twin study. The mild subtype (60% of men and 66% of women) was distinguished by low mean scores on all three scales; the dyssocial subtype (24% of men and 20% of women) by low mean genetic and general environmental scores but high mean dyssocial environmental scores; and the severe subtype (16% of men and 14% of women) by high scores on the genetic and general environmental scales. These subtypes also showed the expected distinctions in clinical characteristics. The severe subtype showed greater comorbid drug dependence and major depression, more treatment seeking, and a higher prevalence of parental alcoholism. The severe subtype also showed significantly greater genetic influence adjusted for overall severity of alcohol dependence (genetic ratio). Only the severe subtype showed a pattern of scale scores and clinical characteristics suggestive of substantial genetic influence. The present study indicates a robustness of the typology originally developed among DSM-III alcohol-dependent Caucasian men by empirical extension of the subtypes to a different sample of Caucasian men and, separately, Caucasian women. The use of this typology may aid in distinguishing between Caucasian alcohol-dependent individuals on the basis of relative genetic influence, enabling genetic, behavioral, and epidemiological investigations to reduce genetic or environmental "noise" and better focus on specific aspects of alcohol dependence.  相似文献   
94.
95.
Five male and four female normal weight research volunteers, participating in 13-day residential studies, received oral fenfluramine (20, 40 mg) or placebo at 09:30 and 17:00. Food intake, performance, and subjective ratings were measured throughout the day. Carbohydrate intake was manipulated by providing lunch meals high (males: 120 g; females: 80 g) or low (males: 25 g; females: 16 g) in carbohydrate on 8 days; on the remaining days subjects self-selected lunch. Total caloric intake (approximately 2800 Kcal) did not differ among the low- and high-carbohydrate, and self-selected lunch conditions when subjects received placebo, indicating caloric compensation. Total carbohydrate intake was significantly less, however, when subjects consumed the low-carbohydrate lunch compared to the other lunch conditions. Fenfluramine significantly decreased total caloric intake (approximately 500 kcal) by decreasing meal size, not number, only when subjects consumed the low-carbohydrate lunch. Fenfluramine was only an effective anorectic drug when subjects consumed a lunch with fewer calories and a lower carbohydrate:protein ratio than self-selected baseline. Also, fenfluramine improved performance on a range of computer tasks and increased ratings of "Alert," "Friendly," and "Talkative," while decreasing ratings of "Tired" and "Irritable."  相似文献   
96.
We examined the laminar and columnar arrangement of projections from different layers of the lateral geniculate nucleus (LGN) to the visual cortex in the cat. In light of recent reports that cytochrome oxidase blobs (which in primates receive specific geniculate inputs) are also found in the visual cortex of cats, the relationship between cytochrome oxidase staining and geniculate inputs in this species was studied. Injections of wheat germ agglutinin-conjugated horseradish peroxidase were made into the anterior "genu" of the LGN, where isoelevation contours of the geniculate layers are distorted due to the curvature of the nucleus. Consequently, anterograde labeling from the various LGN layers was topographically separated across the surface of the cortex, and labeling in a particular isoelevation representation of the cortex could be associated with a specific layer of the LGN. Labeling from the A layers, which contain X and Y cells, was coextensive with layers 4 and 6 in both area 17 and area 18, as previously reported. Labeling from the C layers, which contain Y and W cells, occupied a zone extending from the 4a/4b border to part way into layer 3 in area 17. The labeling extended throughout layer 4 in area 18. There was also labeling in layer 5a and layer 1 in both area 17 and area 18. Except in layer 1, labeling from the C layers was patchy. In the tangential plane, adjacent sections stained for cytochrome oxidase showed that the patches of labeling from the C laminae aligned with the cytochrome oxidase blobs. The cytochrome blobs were visible in layers 3 and 4a, but not in layer 4b in both areas 17 and 18. These results suggest that W cells project specifically to the layer 3 portion of the blobs, while Y cells, at least those of the C layers, project specifically to the layer 4a portion of the blobs in area 17. The heavy synaptic drive of the Y cells is probably the cause of the elevated metabolism, and thus, higher cytochrome oxidase activity, of the blobs.  相似文献   
97.
We describe a heuristic control policy for a general finite‐horizon stochastic control problem, which can be used when the current process disturbance is not conditionally independent of the previous disturbances, given the current state. At each time step, we approximate the distribution of future disturbances (conditioned on what has been observed) by a product distribution with the same marginals. We then carry out dynamic programming (DP), using this modified future disturbance distribution, to find an optimal policy, and in particular, the optimal current action. We then execute only the optimal current action. At the next step, we update the conditional distribution, and repeat the process, this time with a horizon reduced by one step. (This explains the name ‘shrinking‐horizon dynamic programming’). We explain how the method can be thought of as an extension of model predictive control, and illustrate our method on two variations on a revenue management problem. Copyright © 2010 John Wiley & Sons, Ltd.  相似文献   
98.
This paper investigates the fundamental difference between a simple e-tender box and a traditional physical tender box, and highlights a series of security traps created by the functional differences. Based on our findings, we have defined the security requirements for an e-tender submission protocol. We also discuss functional limitations of cryptographic technologies. As a result, two secure e-tender submission protocols are proposed which enable a secure e-tender submission. Protocols are assumed to run under the condition that all tendering parties (principal and tenderers) are dishonest players. Our informal and formal security analysis show that these protocols meet their security goals under well known collusion scenarios. Because security is a process not a product, our approach will have broad industry application for developing secure electronic business processes in areas other than e-tendering.
Colin BoydEmail:
  相似文献   
99.
In constructing local Fourier bases and in solving differential equations with nonperiodic solutions through Fourier spectral algorithms, it is necessary to solve the Fourier Extension Problem. This is the task of extending a nonperiodic function, defined on an interval , to a function which is periodic on the larger interval . We derive the asymptotic Fourier coefficients for an infinitely differentiable function which is one on an interval , identically zero for , and varies smoothly in between. Such smoothed “top-hat” functions are “bells” in wavelet theory. Our bell is (for x ≥ 0) where where . By applying steepest descents to approximate the coefficient integrals in the limit of large degree j, we show that when the width L is fixed, the Fourier cosine coefficients a j of on are proportional to where Λ(j) is an oscillatory factor of degree given in the text. We also show that to minimize error in a Fourier series truncated after the Nth term, the width should be chosen to increase with N as . We derive similar asymptotics for the function f(x)=x as extended by a more sophisticated scheme with overlapping bells; this gives an even faster rate of Fourier convergence  相似文献   
100.
A bistable electromagnetically actuated microvalve was designed, processed, and tested. The valve was designed to control a water flow of 0.05-0.5 μs from a reservoir at a pressure of 1-2000 Pa. The two valve components were fabricated in silicon, the upper piece comprises an electroplated gold coil, and the lower piece is an Ni/Fe alloy beam. The bistable capability was achieved by balancing the elastic forces on the beam with the magnetic forces due to a 46-μm-thick rolled magnetic foil. The design includes the flow through the orifice, squeeze film damping due to beam motion, beam elasticity, and electromagnetics. The microvalve was tested for power consumption, flow rate, time response, Ni/Fe alloy composition, and magnetic foil properties. The valve operates at 1-2 V in both air and water  相似文献   
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