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61.
Carbamoyl-phosphate synthetase (CPSase) consists of a 120-kDa synthetase domain (CPS) that makes carbamoyl phosphate from ATP, bicarbonate, and ammonia usually produced by a separate glutaminase domain. CPS is composed of two subdomains, CPS.A and CPS.B. Although CPS.A and CPS.B have specialized functions in intact CPSase, the separately cloned subdomains can catalyze carbamoyl phosphate synthesis. This report describes the construction of a 58-kDa chimeric CPSase composed of Escherichia coli CPS.A catalytic subdomains and the mammalian regulatory subdomain. The catalytic parameters are similar to those of the E. coli enzyme, but the activity is regulated by the mammalian effectors and protein kinase A phosphorylation. The chimera has a single site that binds phosphoribosyl 5'-pyrophosphate (PRPP) with a dissociation constant of 25 microM. The dissociation constant for UTP of 0.23 mM was inferred from its effect on PRPP binding. Thus, the regulatory subdomain is an exchangeable ligand binding module that can control both CPS.A and CPS.B domains, and the pathway for allosteric signal transmission is identical in E. coli and mammalian CPSase. A deletion mutant that truncates the polypeptide within a postulated regulatory sequence is as active as the parent chimera but is insensitive to effectors. PRPP and UTP bind to the mutant, suggesting that the carboxyl half of the subdomain is essential for transmitting the allosteric signal but not for ligand binding. 相似文献
62.
The Drug Evaluation Classification Program: using ocular and other signs to detect drug intoxication
EM Kosnoski RL Yolton K Citek CE Hayes RB Evans 《Canadian Metallurgical Quarterly》1998,69(4):211-227
BACKGROUND: A systematic approach to determining drug intoxication has been developed for use by police officers. By considering specific physiological signs, trained officers can detect the effects of seven major drug types. METHODS: Officers follow a 12-step testing sequence and evaluate signs such as pupil sizes and responses, eye movements, heart rate, body temperature, mental timing, and balance. A matrix is then used to compare that subject's signs to those that would be produced by the seven types of drugs. If a pattern match is found, the officer concludes that the subject is under the influence of a drug and specifies the drug type. RESULTS: Several field and laboratory validation studies have been conducted using these procedures. In general, officers were 70% to 90% accurate in determining intoxication status and drug classification, but poly-drug use and drug rebound effects can sometimes cause problems in interpretation. CONCLUSION: Ocular and other physiological signs can be used to detect drug intoxication and classify the type of drug taken. Knowledge of the procedures used in the Drug Recognition Program can enable optometrists to serve as consultants to the police and as expert witnesses in cases involving the use of ocular signs that indicate illicit drug use. 相似文献
63.
RY Calne S Thiru P McMaster GN Craddock DJ White DJ Evans DC Dunn BD Pentlow K Rolles 《Canadian Metallurgical Quarterly》1998,9(9):1751-1756
A psychrotrophic yeast, Rhodotorula glutinis KUJ 2731, isolated from soil, effectively produced an extracellular endo-beta-glucanase (EC 3.2.1.4). The enzyme was monomeric, and the molecular mass was about 40,000 Da. The N-terminal amino acid sequence was H-Ser-Leu-Pro- Lys-Leu-Gly-Gly-Val-Asp-Leu-Ala-Gly-Leu-Asp-Ile-Gly-Lys-Asp-Lys-Asn-. alpha-Helix content was calculated to be about 32.6%. The isoelectric point was 8.57. The activation energy was 20.9 kJ/mol, which was much smaller than that of mesophilic enzymes. The enzyme was active at temperatures from 0 to 70 degrees C, with a highest initial velocity at 50 degrees C similar to other psychrotrophic enzymes. The enzyme was inhibited by Hg2+. The enzyme catalyzed hydrolysis of carboxymethyl cellulose with an apparent K(m) of 1.1% and Vmax of 556 mumol/min/mg. Products from the enzymatic hydrolysis of carboxymethyl cellulose by the enzyme were glucose, cellobiose, and cellotriose. The enzyme also catalyzed the transglycosylation of p-nitrophenyl-beta-cellotrioside to cellotetraose. 相似文献
64.
TG Evans W Bonnez HR Soucier T Fitzgerald DC Gibbons RC Reichman 《Canadian Metallurgical Quarterly》1998,39(3):163-173
Criteria for detection of chromosome aberrations by Comparative Genomic Hybridization (CGH) are not standardized and improvement of this part of the analysis is of paramount importance to the applicability of the technique. The aim of this work was to suggest CGH detection criteria that increase the specificity and sensitivity and at the same time include chromosome regions previously excluded from CGH analysis. We analyzed 33 hybridizations with normal DNA and modified our CGH software in order to use a selection of these normal analyses as a model for interpretation of analyses of unknown samples. This approach was successfully tested on 14 samples with known aberrations. 相似文献
65.
Endotoxaemia is a leading cause of death among horses. Thrombocytopenia is a common finding in clinical and experimentally-induced cases of endotoxaemia and can lead to coagulopathies, including disseminated intravascular coagulopathy which is usually fatal. In this study it was shown that endotoxin (3 ng ml-1 to 25 micrograms ml-1) can aggregate equine platelets in heparinised whole blood in vitro. The endotoxin-induced aggregation (EIA) was shown to be dependent on the presence of leucocytes in the blood and did not occur when detoxified endotoxin was used, suggesting that lipid A was necessary for the response. Aspirin (1 mmol litre-1) had no effect on EIA whereas apyrase (40 micrograms ml-1) completely abolished it and CV3988 (3 to 30 mumol litre-1) (a competitive antagonist of platelet-activating factor) inhibited the response in a concentration-dependent manner. It is concluded that endotoxin activates equine platelets at low concentrations through an indirect mechanism that involves calcium, leucocytes, adenine nucleotides and platelet-activating factor. 相似文献
66.
Henning H. Mikkelsen Jens Oddershede John R. Sabin Ejvind Bonderup 《Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms》1995,100(4):451-457
We derive a Bethe formula for the stopping of swift ions by target molecules oriented with respect to the beam. The theory is characterized by a directional mean excitation energy formed from transition energies and dipole matrix elements. The expression for the mean excitation energy is similar to the one for an isotropic sample but the dipole matrix elements corresponding to the various transition moment directions carry unequal weights which depend on the orientation of the molecule with respect to the beam. For a large class of molecules, the logarithm of the mean excitation energy is linear in sin2 θ, where θ denotes the angle between the beam and the principal molecular axis. We illustrate the properties of the theory in the simple case of a diatomic molecule. 相似文献
67.
Experimental studies have been performed on ceramic matrix composite (CMC) I-sections, which typify joint designs for CMC components. Axial loads and moments have been applied to activate delamination mechanisms. The maximum load bearing capacity has large variability, governed by the severity of manufacturing flaws located in the transition region of the I-section. This variability leads to an unsatisfactory design situation. Delaminations that form from these flaws arrest and behave in a stable manner, subject to a remanent load bearing capacity. This remanent capacity has minimal variability. Hence, design based on the remanent load would be robust. An expression for this design criterion is presented. 相似文献
68.
Evans WA 《Applied ergonomics》1990,21(2):135-142
A laboratory study was undertaken to assess the relationship between the maximal voluntary isometric strength (MVIS) of a group of Hong Kong Cantonese males and recommended limiting values for lifting proposed in the Work Practices Guide for Manual Lifting (NIOSH, 1981). Forty-one male subjects were required to apply a 'free-style' vertical 'lift' force to a horizontal bar located 150 mm from the ground. Forces were applied with the horizontal location of the midpoint of the ankles at 200, 400, 600 and 800 mm from the bar. The results were compared with the Maximal Permissible Limit (MPL) and the Action Limit (AL) values proposed in the NIOSH guide. The results showed that the mean MVIS of the Hong Kong subjects lay between the MPL and AL when the load was 200 mm and 400 mm from the ankles, but was significantly below the AL at 600 mm. At 800 mm more than half of the subjects were unable to apply any measurable positive vertical force. The compressive force at the L5/S1 disc of four subjects was estimated using a static biomechanical model. The relationship between the disc pressure and the force exerted was largely in accordance with NIOSH guide values. The results are discussed in terms of differences in subject population and lifting technique. Comments on the applicability of the NIOSH standards internationally, are also presented. 相似文献
69.
70.
Prof. Alessia Carocci Dr. Mariagrazia Roselli Prof. Roberta Budriesi Dr. Matteo Micucci Prof. Jean-François Desaphy Dr. Concetta Altamura Dr. Maria Maddalena Cavalluzzi Dr. Maddalena Toma Dr. Giovanna Ilaria Passeri Dr. Gualtiero Milani Dr. Angelo Lovece Prof. Alessia Catalano Dr. Claudio Bruno Dr. Annalisa De Palma Prof. Filomena Corbo Prof. Carlo Franchini Prof. Solomon Habtemariam Prof. Giovanni Lentini 《ChemMedChem》2021,16(3):578-588
Under the hypothesis that cardioprotective agents might benefit from synergism between antiarrhythmic activity and antioxidant properties, a small series of mexiletine analogues were coupled with the 2,2,5,5-tetramethylpyrroline moiety, known for its antioxidant effect, in order to obtain dual-acting drugs potentially useful in the protection of the heart against post-ischemic reperfusion injury. The pyrroline derivatives reported herein were found to be more potent as antiarrhythmic agents than mexiletine and displayed antioxidant activity. The most interesting tetramethylpyrroline congener, a tert-butyl-substituted analogue, was at least 100 times more active as an antiarrhythmic than mexiletine. 相似文献