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991.
Challal S Bohni N Buenafe OE Esguerra CV de Witte PA Wolfender JL Crawford AD 《Chimia》2012,66(4):229-232
The rapid acquisition of structural and bioactivity information on natural products (NPs) at the sub- milligram scale is key for performing efficient bioactivity-guided isolations. Zebrafish offer the possibility of rapid in vivo bioactivity analysis of small molecules at the microgram scale - an attractive feature when combined with high-resolution fractionation technologies and analytical methods such as UHPLC-TOF-MS and microflow NMR. Numerous biomedically relevant assays are now available in zebrafish, encompassing most indication areas. Zebrafish also provide the possibility to screen bioactive compounds for potential hepato-, cardio-, and neurotoxicities at a very early stage in the drug discovery process. Here we describe two strategies using zebrafish bioassays for the high-resolution in vivo bioactivity profiling of medicinal plants, using either a one-step or a two-step procedure for active compound isolation directly into 96-well plates. The analysis of the microfractions by microflow NMR in combination with UHPLC-TOF-MS of the extract enables the rapid dereplication of compounds and an estimation of their microgram quantities for zebrafish bioassays. Both the one-step and the two-step isolation procedures enable a rapid estimation of the bioactive potential of NPs directly from crude extracts. In summary, we present an in vivo , microgram-scale NP discovery platform combining zebrafish bioassays with microscale analytics to identify, isolate and evaluate pharmacologically active NPs. 相似文献
992.
Daniele Suzzi Gregor Toschkoff Stefan Radl Daniel Machold Simon D. Fraser Benjamin J. Glasser Johannes G. Khinast 《Chemical engineering science》2012,69(1):107-121
Tablet coating is a common pharmaceutical technique of applying a thin polymer-based film to a tablet or a granule containing active pharmaceutical ingredients (APIs). Inter- and intra-tablet variability of film coating is a critical issue in the production of solid oral dosage forms. In fact, inhomogeneity in the coating thickness can lead to significant variations in the delivery rate of active pharmaceutical ingredients and compromise the functional attributes of the tablet film. Although attempts have been made to use numerical approaches to analyze this complex problem, at present the uniformity of coating thickness is difficult to predict without expensive experimental work.The aim of this work is to analyze and understand the effects of tablet form and fill volume on the intra-tablet coating variability in a semi-continuous coating device. To this end, the Discrete Element Method was used to numerically reproduce the tablet motion inside a chamber of the coating pan. First, the material attributes of a sample placebo tablet were experimentally quantified in detail. Thereafter, three different tablet shapes, namely bi-convex, oval, and round, were modeled by means of the “glued spheres” method. The effect of three different fill volumes was then analyzed in terms of RT of the tablets under the coating spray, leading to a quantification of the intra-tablet coating variability for each particle shape. A detailed analysis of the tablets' velocities, both translational and rotational, on top of the tablet bed is presented. These results help to understand the dynamical behavior of the tablets under a spray gun that is essential for a satisfactory intra-tablet coating homogeneity. Finally, the various behaviors observed during the numerical simulations were addressed through a detailed analysis of the tablets' flow on the bed in terms of mean velocities and granular temperatures. The aim of this work is to demonstrate how a numerical simulation may be used for the development and design of continuous pharmaceutical tablet coating processes. 相似文献
993.
Continuous geodetic time-transfer analysis methods 总被引:1,自引:0,他引:1
Dach R Schildknecht T Hugentobler U Bernier LG Dudle G 《IEEE transactions on ultrasonics, ferroelectrics, and frequency control》2006,53(7):1250-1259
We address two issues that limit the quality of time and frequency transfer by carrier phase measurements from the Global Positioning System (GPS). The first issue is related to inconsistencies between code and phase observations. We describe and classify several types of events that can cause inconsistencies and observe that some of them are related to the internal clock of the GPS receiver. Strategies to detect and overcome time-code inconsistencies have been developed and implemented into the Bernese GPS Software package. For the moment, only inconsistencies larger than the 20 ns code measurement noise level can be detected automatically. The second issue is related to discontinuities at the day boundaries that stem from the processing of the data in daily batches. Two new methods are discussed: clock handover and ambiguity stacking. The two approaches are tested on data obtained from a network of stations, and the results are compared with an independent time-transfer method. Both methods improve the stability of the transfer for short averaging times, but there is no benefit for averaging times longer than 8 days. We show that continuous solutions are sufficiently robust against modeling and preprocessing errors to prevent the solution from accumulating a permanent bias. 相似文献
994.
Waizy H Weizbauer A Maibaum M Witte F Windhagen H Lucas A Denkena B Meyer-Lindenberg A Thorey F 《Journal of materials science. Materials in medicine》2012,23(3):649-655
Magnesium alloys have been in the focus of research in recent years as degradable biomaterial. The purpose of this study was
the biomechanical characterisation of MgCa0.8-screws. The maximum pull out force of screws was determined in a synthetic bone
without corrosion and after fixed intervals of corrosion: 24, 48, 72 and 96 h. This in vitro study has been carried out with
Hank’s solution with a flow rate corresponding to the blood flow in natural bone. A maximum pull out force (Fmax) of 201.5 ± 9.3 N was measured without corrosion. The biomechanical parameter decreased by 30% after 96 h in corrosive medium
compared to the non-corrosion group. A maximum load capacity of 28 ± 7.6 N/h was determined. Our biomechanical data suggests
that this biodegradable screw provides a promising bone-screw-fixation and has great potential for medical application. 相似文献
995.
Plecenik T Robin S Gregor M Truchly M Lang S Gandhi A Zahoran M Laffir F Soulimane T Vargova M Plesch G Kus P Plecenik A Tofail SA 《Journal of materials science. Materials in medicine》2012,23(1):47-50
Micro-domains of modified surface potential (SP) were created on hydroxyapatite films by direct patterning by mid-energy focused electron beam, typically available as a microprobe of Scanning Electron Microscopes. The SP distribution of these patterns has been studied on sub-micrometer scale by the Kelvin Probe Force Microscopy method as well as lysozyme adsorption. Since the lysozyme is positively charged at physiological pH, it allows us to track positively and negatively charged areas of the SP patterns. Distribution of the adsorbed proteins over the domains was in good agreement with the observed SP patterns. 相似文献
996.
In this Letter, we present the size effects on charge conduction in InN nanowires by comprehensive transport studies supported by theoretical analysis. A consistent model for highly degenerate narrow gap semiconductor nanowires is developed. In contrast to common knowledge of InN, there is no evidence of an enhanced surface conduction, however, high intrinsic doping exists. Furthermore, the room-temperature resistivity exhibits a strong increase when the lateral size becomes smaller than 80 nm and the temperature dependence changes from metallic to semiconductor-like. This effect is modeled by donor deactivation due to dielectric confinement, yielding a shift of the donor band to higher ionization energies as the size shrinks. 相似文献
997.
Xavier Le Guével Christian Spies Nicole Daum Gregor Jung Marc Schneider 《Nano Research》2012,5(6):379-387
A panel of silver nanoclusters (Ag NCs) protected by glutathione has been produced by collecting them on a plastic surface during an interfacial etching process. Blue-green, yellow and red emitting Ag NCs with size smaller than 2 nm exhibited distinct fluorescence properties (both emission and lifetime). In particular, the yellow emitting Ag NCs were found to reach a very high quantum yield of over 60% with a monoexponential fluorescence lifetime. These labels show no bleaching and high photostability over time and a high stability for a wide range of pH values. Cytotoxicity tests demonstrated the viability in the presence of of these luminescent probes even at high concentration (1 mg/mL). Cell studies confirmed the uptake of Ag NCs in epithelial lung cancer cells by an endocytotic process. These results show the high potential of fluorescent noble metal nanoclusters for biolabeling and imaging as alternatives to the standard fluorescent probes such as quantum dots or organic dyes. 相似文献
998.
Edgar Luttmann Dr. Jürgen Ludwig Dr. Anja Höffle‐Maas Dr. Marek Samochocki Dr. Alfred Maelicke Prof. Dr. Gregor Fels Prof. Dr. 《ChemMedChem》2009,4(11):1874-1882
Current treatments of Alzheimer's disease include the allosteric potentiation of nicotinic acetylcholine receptor (nAChR) response. The location of the binding site for allosteric potentiating ligands (APLs) within the receptor is not yet fully understood. Based on homology models for the ligand binding domain of human α7, human α4β2, and chicken α7 receptors, as well as blind docking experiments with galanthamine, physostigmine, codeine, and 5HT, we identified T197 as an essential element of the APL binding site at the outer surface of the ligand binding domain (LBD) of nAChR. We also found the previously known galanthamine binding site in the region of K123 at the inside of the receptor funnel, which, however, was shown to not be part of the APL site. Our results are verified by site‐directed mutagenesis and electrophysiological experiments, and suggest that APL and ACh bind to different sites on nicotinic receptors and that allosteric potentiation may arise from a direct interplay between both these sites. 相似文献
999.
Ein wesentliches Element der hygrothermischen Charakterisierung von Baustoffen ist der Trocknungsversuch. Im Gegensatz zu anderen Feuchtetransportexperimenten wie dem Diffusionsversuch oder dem Wasseraufnahmeexperiment ist es bislang nicht möglich, aus der Trocknung einen einfachen Kennwert abzuleiten. In vielen Fällen, beispielsweise in der Interaktion von Forschung und Industrie, aber auch beim praktischen Vergleich bzw. der Auswahl geeigneter Baustoffe wäre ein solcher Kennwert jedoch wünschenswert. Im vorliegenden Artikel wird zunächst die Bedeutung des Trocknungsversuches für die hygrische Charakterisierung von Baustoffen herausgestellt, aus der sich das Bestreben ableitet, das Trocknungsverhalten zu standardisieren und einen Einzahlen‐Materialkennwert zu definieren. Nach einer die verschiedenen Einflussfaktoren der Trocknung differenzierenden Einleitung werden bestehende Ansätze für die Standardisierung des Trocknungsverlaufes bzw. die Ableitung eines Trocknungskoeffizienten vorgestellt. Die einhergehenden Probleme werden diskutiert und weitere Möglichkeiten evaluiert. Ein einfacher Trocknungskoeffizient, der sich aus dem Trocknungsverlauf ableiten lässt, wird definiert. Die Korrelation dieses Koeffizienten mit dem Wasseraufnahmekoeffizienten und dem Dampfdiffusionswiderstand wird analysiert. Sein zusätzlicher Informationsgehalt wird in diesem Zusammenhang kritisch hinterfragt. Im Ergebnis steht die Definition des Trocknungskoeffizienten als ein neuer, unabhängiger Materialkennwert, der die Feuchtetransporteigenschaften im Übergang zwischen hygroskopischem und gesättigtem Transport beschreibt. Mit diesem Kennwert ist es möglich, Baustoffe einfach und schnell hinsichtlich ihres Trocknungsverhaltens zu unterscheiden und zu beurteilen, was insbesondere bei feuchtesensitiven Materialien von Bedeutung ist. A drying coefficient for building materials. The drying experiment is an important element of the hygrothermal characterisation of building materials. Contrary to other moisture transport experiments as the vapour diffusion and the water absorption test, it is until now not possible to derive a simple coefficient for the drying. However, in many cases such a coefficient would be highly appreciated, e.g. in interaction of industry and research or for the distinction and selection of suitable building materials throughout design and practise. This article first highlights the importance of drying experiments for hygrothermal characterisation of building materials on which the attempt is based to standardize the drying experiment as well as to derive a single number material coefficient. The drying itself is briefly reviewed and existing approaches are discussed. On this basis, possible definitions are evaluated. Finally, a drying coefficient is defined which can be determined based on measured drying data. The correlation of this coefficient with the water absorption and the vapour diffusion coefficient is analyzed and its additional information content is critically challenged. As result, a drying coefficient has been derived and defined as a new and independent material parameter. It contains information about the moisture transport properties throughout the wide range of moisture contents from hygroscopic up to saturation. With this new and valuable coefficient, it is now possible to distinguish and select building materials quickly and easily by means of their drying behaviour. This is particularly important for moisture sensitive materials. 相似文献
1000.
Christian Gregor Dieseldorff 《电子与电脑》2009,(10)
根据SEMI(国际半导体设备材料产业协会)最新发布的全球晶圆厂报告,预估2010年全球晶圆厂资本支出将达到240亿美元,较今年增长64%. 相似文献