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101.
Lenssen K Jantscheff P von Kiedrowski G Massing U 《Chembiochem : a European journal of chemical biology》2002,3(9):852-858
Here we describe the first synthesis-screening approach for the identification and optimization of new cationic lipids for gene transfer in various cell lines. Combinatorial solid-phase chemistry was used to synthesize a library of new cationic lipids based on 3-methylamino-1,2-dihydroxypropane as the polar, cationic lipid part. As the nonpolar lipid part, different hydrocarbon chains were bound to the amino group of the scaffold and the amino group was further methylated to afford constantly cationic lipids. Lipids were synthesized in both configurations and as racemates, and the counter ions were also varied. By using a fully automated transfection screening method and COS-7 cells, the cationic lipid N,N-ditetradecyl-N-methyl-amino-2,3-propanediol (KL-1-14) was identified as a candidate lipid for the development of an improved transfection reagent. Screening the transfection properties of KL-1-14 in numerous combinations with the helper lipids dioleoylphosphatidylethanolamine (DOPE) and cholesterol (Chol) revealed that Chol is the most suitable helper lipid and the best KL-1-14/Chol ratio is 0.5-0.7. Compared to the standard transfection lipid N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl sulfate (DOTAP), transfection efficiency was improved by a factor of about 40. Furthermore, by using R- and S-configured KL-1-14, it could be shown that the configuration of the lipids had no significant influence on its transfection efficiency. The highest transfection efficiencies were achieved with chloride as the counter ion. The new lipofection reagent was further tested to transfect the cell lines MDA-MB-468, MCF-7, MDCK-C7, and primary dentritic cells (DC), which are important for the development of new anticancer gene therapy strategies. Even in these cells, KL-1-14/Chol (1:0.6) had improved transfection efficiencies, which were about two to four times higher than for DOTAP. 相似文献
102.
Andreas BeckmannFranz Nierlich Tim PöpkenDieter Reusch Claudia von ScalaAxel Tuchlenski 《Chemical engineering science》2002,57(9):1525-1530
The objective of this paper is to illustrate process design from the industrial point of view for a heterogeneous reactive distillation exemplified by the decomposition of MTBE. Based on thermodynamics a plausible column concept is suggested. Open questions concerning scale-up of structured catalytic packings are discussed on the basis of experiments in the lab and pilot plant scale. Lab scale experiments were modelled satisfactorily with an equilibrium stage approach. In order to perform the scale-up from lab to pilot scale with the equilibrium stage approach the reaction rate constant had to be reduced significantly. Incomplete catalyst wetting due to maldistribution effects or mass transfer phenomena might be possible reasons. 相似文献
103.
The gasification reaction of fir charcoal with CO2 was studied by isothermal thermogravimetric analysis under kinetic control. The derived reaction rate (r=dX/dt) as a function of the converted carbon mass (X) was compared with random pore model predictions and found to be much higher at elevated conversion levels than predicted by theory. Similar enhanced reaction rate behaviour was evidenced after removing the natural alkali catalyst from the charcoal by acid washing, suggesting that with untreated charcoal the late reaction rate contribution stems from both, catalytic and additional structure effects. Literature attributes the unpredicted late reaction rate behaviour to the disintegration of the porous char particle into small fragments, which, in line with percolation theory predictions, seems to occur only after a critical conversion level has been reached. However, our gasification data reveal a gradual rise in the charcoal reactivity thereafter, suggesting a breaking up (embrittlement) of the solid phase accompanied by the exposure of fresh surface area from fracturing. The original random pore model derivation given by Bhatia and Perlmutter is extended to account also for these peculiarities and the resulting kinetic relation described our reaction rate data well over the entire conversion range. 相似文献
104.
The heterogeneous enantioselective hydrogenation of activated ketones over chirally modified platinum is reviewed with emphasis on identifying the role of the various species observed in this catalytic system. The past years have witnessed a continuous broadening of the scope of this catalytic system including new reactants and modifiers affording over 97% ee. New reaction pathways have been uncovered and the kinetic and mechanistic studies have been faced with a number of complicating factors caused by spectator species and interactions in solution and on the Pt surface. The previously proposed mechanistic models are critically assessed in the light of these new findings. 相似文献
105.
Dr. Raysa Khan Tareque Dr. Storm Hassell-Hart Dr. Tobias Krojer Dr. Anthony Bradley Dr. Srikannathasan Velupillai Dr. Romain Talon Dr. Michael Fairhead Dr. Iain J. Day Kamlesh Bala Dr. Robert Felix Dr. Paul D. Kemmitt Prof. Paul Brennan Prof. Frank von Delft Dr. Laura Díaz Sáez Prof. Kilian Huber Prof. John Spencer 《ChemMedChem》2020,15(24):2513-2520
Combined photochemical arylation, “nuisance effect” (SNAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with SNAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified. 相似文献
106.
Pauline Hibon Heinz von Seggern Hsin-Rong Tseng Christoph Leonhard Manuel Hamburger Gaëlle Béalle 《应用聚合物科学杂志》2020,137(29):48895
Interface control remains a top challenge of solution-processed organic light emitting diodes (OLED) stacks since the device performance heavily relies on it. Film stability of an inkjet deposited and crosslinked layer against subsequent exposure to a suitable inkjet printed solvent has been investigated. Impact of processing solvent (solvent used to prepare the polymer layer) on solution-cast thin film properties has already been shown for polymer films. To our knowledge, this study is the first one analyzing thin films stability against solvent exposure using technology relevant materials processed via inkjet printing (IJP). The outcome of this research showed that the stability of the crosslinked films is affected by the solvent used for ink formulation. These findings are of great interest for multilayered semiconductors devices, such as OLEDs, field-effect transistors and dye-sensitized solar cells. Differential scanning calorimetry (DSC) was used to quantify the efficiency of the polymer crosslinking reaction in pure powder and in thin films, as processed from different solvents. Crosslinking efficiency measured by DSC correlated well with the deformation induced by the solvent and observed on layer surfaces. The interaction in solution between polymer and solvent has also been evaluated to explain its impact on thin film stability against successive solvent printing. © 2020 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48895. 相似文献
107.
Nicolas Dolder Prof. Dr. Christoph von Ballmoos 《Chembiochem : a European journal of chemical biology》2020,21(15):2219-2224
Enzyme-mediated proton transport across biological membranes is critical for many vital cellular processes. pH-sensitive fluorescent dyes are an indispensable tool for investigating the molecular mechanism of proton-translocating enzymes. Here, we present a novel strategy to entrap pH-sensitive probes in the lumen of liposomes that has several advantages over the use of soluble or lipid-coupled probes. In our approach, the pH sensor is linked to a DNA oligomer with a sequence complementary to a second oligomer modified with a lipophilic moiety that anchors the DNA conjugate to the inner and outer leaflets of the lipid bilayer. The use of DNA as a scaffold allows subsequent selective enzymatic removal of the probe in the outer bilayer leaflet. The method shows a high yield of insertion and is compatible with reconstitution of membrane proteins by different methods. The usefulness of the conjugate for time-resolved proton pumping measurements was demonstrated by using two large membrane protein complexes. 相似文献
108.
Dr. Bettina Sommer Dr. Holger von Moeller Martina Haack Dr. Farah Qoura Clemens Langner Dr. Gleb Bourenkov Dr. Daniel Garbe Dr. Bernhard Loll Prof. Dr. Thomas Brück 《Chembiochem : a European journal of chemical biology》2015,16(1):110-118
Isobutanol is deemed to be a next‐generation biofuel and a renewable platform chemical. 1 Non‐natural biosynthetic pathways for isobutanol production have been implemented in cell‐based and in vitro systems with Bacillus subtilis acetolactate synthase (AlsS) as key biocatalyst. 2 – 6 AlsS catalyzes the condensation of two pyruvate molecules to acetolactate with thiamine diphosphate and Mg2+ as cofactors. AlsS also catalyzes the conversion of 2‐ketoisovalerate into isobutyraldehyde, the immediate precursor of isobutanol. Our phylogenetic analysis suggests that the ALS enzyme family forms a distinct subgroup of ThDP‐dependent enzymes. To unravel catalytically relevant structure‐function relationships, we solved the AlsS crystal structure at 2.3 Å in the presence of ThDP, Mg2+ and in a transition state with a 2‐lactyl moiety bound to ThDP. We supplemented our structural data by point mutations in the active site to identify catalytically important residues. 相似文献
109.
Cover Picture: Selective Inhibitors of the Protein Tyrosine Phosphatase SHP2 Block Cellular Motility and Growth of Cancer Cells in vitro and in vivo (ChemMedChem 5/2015) 下载免费PDF全文
110.
Ina Eibl Daniela von der Haar Marius Jesdinszki Andreas Stäbler Markus Schmid Horst‐Christian Langowski 《应用聚合物科学杂志》2018,135(25)
In order to minimize the utilization of non‐renewable fossil resources, novel polymer sources for food packaging are being investigated. Micellar Lupin Protein (MLP), produced by dilution precipitation has great potential as functional laminating adhesive due to its high adhesion‐ and oxygen‐barrier properties. Formulations of MLP are used as laminating adhesive between high density‐polyethylene foil and paper as well as coating for poly(ethylene terephthalate) foil. The application of glycerol, sorbitol and combinations thereof as plasticizers are being investigated. Adhesive behavior as well as oxygen‐ and water vapor barrier properties were tested. The addition of both plasticizers enabled the preparation of processable coatings showing coherent and homogeneous morphology with improved adhesive behavior and oxygen barrier. When using sorbitol oxygen permeation coefficients of 0.93 cm3 (STP) 100 µm m?2 d?1 bar?1 were achieved. The laminates containing only sorbitol provided adhesion properties comparable to standard polyurethane laminates with cohesion failure in 100% of the by T‐Peel‐Test examined cases. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46383. 相似文献