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排序方式: 共有79条查询结果,搜索用时 15 毫秒
1.
Martijn J. C. van der Lienden Jan Aten Andr R. A. Marques Ingeborg S. E. Waas Per W. B. Larsen Nike Claessen Nicole N. van der Wel Roelof Ottenhoff Marco van Eijk Johannes M. F. G. Aerts 《International journal of molecular sciences》2021,22(5)
The lysosomal storage disease Niemann–Pick type C (NPC) is caused by impaired cholesterol efflux from lysosomes, which is accompanied by secondary lysosomal accumulation of sphingomyelin and glucosylceramide (GlcCer). Similar to Gaucher disease (GD), patients deficient in glucocerebrosidase (GCase) degrading GlcCer, NPC patients show an elevated glucosylsphingosine and glucosylated cholesterol. In livers of mice lacking the lysosomal cholesterol efflux transporter NPC1, we investigated the expression of established biomarkers of lipid-laden macrophages of GD patients, their GCase status, and content on the cytosol facing glucosylceramidase GBA2 and lysosomal integral membrane protein type B (LIMP2), a transporter of newly formed GCase to lysosomes. Livers of 80-week-old Npc1−/− mice showed a partially reduced GCase protein and enzymatic activity. In contrast, GBA2 levels tended to be reciprocally increased with the GCase deficiency. In Npc1−/− liver, increased expression of lysosomal enzymes (cathepsin D, acid ceramidase) was observed as well as increased markers of lipid-stressed macrophages (GPNMB and galectin-3). Immunohistochemistry showed that the latter markers are expressed by lipid laden Kupffer cells. Earlier reported increase of LIMP2 in Npc1−/− liver was confirmed. Unexpectedly, immunohistochemistry showed that LIMP2 is particularly overexpressed in the hepatocytes of the Npc1−/− liver. LIMP2 in these hepatocytes seems not to only localize to (endo)lysosomes. The recent recognition that LIMP2 harbors a cholesterol channel prompts the speculation that LIMP2 in Npc1−/− hepatocytes might mediate export of cholesterol into the bile and thus protects the hepatocytes. 相似文献
2.
The actuator disc is the oldest representation of a rotor, screw or propeller. Performance prediction is possible by applying momentum theory, giving integrated values for power and velocity. Computational fluid dynamics has provided much more flow details, but a full potential flow solution zooming in on these flow details was still absent. With the wake boundary discretized by vortex rings, flow states for energy extracting discs have been obtained for thrust coefficients up to 0.998. Boundary conditions are met with an accuracy of a few ‰. Results from momentum theory are confirmed. Most rotor design codes use momentum theory in annulus or differential form, assuming that the axial velocity vx at the disc is uniform. However, the absolute velocity | v | is found to be uniform, and arguments for this are presented. The non‐uniformity of vx is an inherent part of the flow solution caused by, in terms of momentum theory, the pressure acting at the annuli. This makes the annuli not independent from each other as assumed in current design codes. Although this was already known, it is now confirmed up to the highest thrust coefficients. Optimizing a rotor design should be carried out for the non‐uniform distribution of vx. To enable this, an equation for the non‐uniformity as function of thrust and radial position is presented, being a surface‐fit to the calculated data. Qualitatively, the non‐uniform distribution does the same as the Prandtl–Glauert–Shen tip correction applied to a uniform distribution. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
3.
Martijn Kuik Gert‐Jan A. H. Wetzelaer Jurre G. Laddé Herman T. Nicolai Jurjen Wildeman Jörgen Sweelssen Paul W. M. Blom 《Advanced functional materials》2011,21(23):4502-4509
The effect of on‐chain ketone defects on the charge transport of the polyfluorene derivative poly(9,9‐dioctylfluorene) (PFO) is investigated. Using MoO3 as ohmic hole contact, the hole transport in a pristine PFO diode is observed to be limited by space‐charge, whereas fluorenone contaminated PFO (PFO‐F) is shown to be trap limited by the occurrence of an exponential trap distribution with a trap depth of 0.18 eV. The electron transport in PFO is also observed to be trap limited, but in order to describe the electron transport of PFO‐F, an additional trap level with a depth of 0.46 eV must be introduced. The obtained energy levels of the fluorenone trapping sites are in close agreement with cyclic voltammetry (CV) measurements reported in literature. As a result, the fluorenone defects are shown to simultaneously act as hole‐ and electron trap. Moreover, through ideality factor measurements, the green emission associated with these defects is observed to originate from trap‐assisted recombination. 相似文献
4.
In this paper, we carry out a meta-analysis of recent studies into the costs of greenhouse gas mitigation policies that aim at the long-term stabilisation of these gases in the atmosphere. We find the cost estimates of the studies to be sensitive to the stringency of the stabilisation target, the assumed emissions baseline, the way in which the time profile of emissions is determined in the model, the choice of control variable (CO2 only versus multigas), the number of regions and energy sources in the model and, to a lesser degree, the scientific “forum” in which the study was developed. We find that marginal abatement costs of the stringent long-term targets that are currently considered by the European Commission are still very uncertain but might exceed the costs that have been suggested by recent policy assessments. 相似文献
5.
Roelof K Brouwer 《Soft Computing - A Fusion of Foundations, Methodologies and Applications》2005,9(10):749-756
This research is concerned with a gradient descent training algorithm for a target network that makes use of a helper feed-forward network (FFN) to represent the cost function required for training the target network. A helper FFN is trained because the cost relation for the target is not differentiable. The transfer function of the trained helper FFN provides a differentiable cost function of the parameter vector for the target network allowing gradient search methods for finding the optimum values of the parameters. The method is applied to the training of discrete recurrent networks (DRNNs) that are used as a tool for classification of temporal sequences of characters from some alphabet and identification of a finite state machine (FSM) that may have produced all the sequences. Classification of sequences that are input to the DRNN is based on the terminal state of the network after the last element in the input sequence has been processed. If the DRNN is to be used for classifying sequences the terminal states for class 0 sequences must be distinct from the terminal states for class 1 sequences. The cost value to be used in training must therefore be a function of this disjointedness and no more. The outcome of this is a cost relationship that is not continuous but discrete and therefore derivative free methods have to be used or alternatively the method suggested in this paper. In the latter case the transform function of the helper FFN that is trained using the cost function is a differentiable function that can be used in the training of the DRNN using gradient descent.Acknowledgement. This work was supported by a discovery grant from the Government of Canada. The comments made by the reviewers are also greatly appreciated and have proven to be quite useful. 相似文献
6.
Today's lifecycle of new and emerging products, increase in labour costs in developed countries and user's expectations or behaviours including frequently upgrading items with latest features, influence the growth rate of product disposal to landfill. To reduce the negative impact on the environment, global manufacturers need to take responsibility for designing sustainable products and implementing cleaner production systems for 3R operations (3R–Reuse/Remanufacture/Recycle). Nevertheless, there is still a lack of comprehensive measures for assessing product returns with recovery settings. In this paper, a framework for performance evaluation using design for six sigma methodology is developed to estimate utilisation value of a manufactured product with recovery settings, which accounts for total recovery cost, manufacturing lead-time, minimisation for landfill waste and quality characteristic. Finally, a numerical example based on these performance attributes to assess product utilisation value is presented. 相似文献
7.
A. Brent Bollong B.Sc. Roelof P. Bult M.Sc. 《JOM Journal of the Minerals, Metals and Materials Society》1989,41(7):39-41
High-purity tellurium is used in the preparation of II–VI compounds, particularly CdTe and Cdx Hg1?x Te. Distillation of tellurium under low-pressure H2 reduces the concentrations of iron and silicon. The addition of CdTe to tellurium prior to zone refining, in a quantity less than the eutectic concentration, has been observed to change the segregation behavior of Ca, K, Ga and As, which enables more efficient refining. Emission spectroscopy, spark source mass spectroscopy and the evaluation of Cd0.21Hg0.79 Te have been used to characterize these effects. 相似文献
8.
An improved physical understanding of the rotor aerodynamics of a horizontal axis wind turbine (HAWT) is required to reduce the uncertainties associated with today's design codes. Wind tunnel experiments contribute to increased knowledge and enable validation and construction of models. The present study focuses on the near‐wake of a model HAWT in both axial and yawed flow conditions. At three downstream planes parallel to the rotor plane, single‐sensor hot‐film traverses are made. The phase‐locked unsteady three‐dimensional flow velocity vector is determined by a novel data reduction method. A series of two papers discusses the near‐wake aerodynamics of a model HAWT. The main goals are to obtain a detailed understanding of the near‐wake development and to arrive at a base for model construction and validation. The first paper presents the experimental setup, data reduction and the results for the baseline case (axial flow conditions). In the second paper, the results for the yawed flow cases are presented and the effect of yaw misalignment on the near‐wake development is discussed. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
9.
The effects of 0-, 2-, and 24-hr wheel access on the pattern of running, feeding, and weight were explored over 24 days in 3 groups of 8 male rats. Both 2 and 24 hr of wheel access suppressed feeding by about 15% for about 8 days before feeding gradually returned to normal. Weight in these 2 groups was similar and was suppressed for the 24 days. Like the pattern seen with drug self-administration (S. H. Ahmed & G. F. Koob, 1998, 1999), running levels stayed low with short, 2-hr daytime wheel access, but with long, 24-hr access, rats' running escalated over days to chronically high levels. These results may have relevance for the understanding of addiction and anorexia nervosa. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
10.