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991.
Lo KM Zhang J Sun Y Morelli B Lan Y Lauder S Brunkhorst B Webster G Hallakou-Bozec S Doaré L Gillies SD 《Protein engineering, design & selection : PEDS》2005,18(1):1-10
Leptin plays a central role in the homeostasis of body weight through its regulatory effects on appetite and energy expenditure, yet in trials as a therapeutic agent for the treatment of obesity in humans it has been disappointing. The poor clinical efficacy of leptin results from its short circulating half-life, low potency and poor solubility, necessitating large and frequent doses to obtain even modest clinical benefit. Engineered Fc-leptin immunofusins, consisting of the Fc fragment of an immunoglobulin gamma chain followed by leptin, exhibit improved pharmacological properties with very consistent and potent biological activities. Furthermore, in extending the circulating half-life of the protein in vivo from a few minutes for leptin to many hours for Fc-leptin, these proteins have the potential to reduce drastically the dosage and frequency of administration required to obtain clinical benefit. The results of this study show that the engineered leptin immunofusins described here have significantly enhanced pharmacological properties in comparison with the recombinant leptin that was used in clinical trials. As such, they could represent an important step towards a therapeutically superior form of leptin if the disappointing performance of leptin in early clinical trials was due to its poor pharmacological properties rather than any conceptual weakness in the strategy of using leptin for the treatment of obesity and its related disorders. 相似文献
992.
Sang-Gon Kim Jong-Sung Park Jae-Sul An Kug Sun Hong Hyunho Shin Hyungsun Kim 《Journal of the American Ceramic Society》2006,89(3):902-907
Various types of crystalline ceramic fillers (TiO2 , ZrO2 , Al2 O3 , MgO, and cordierite) were added to BaO–ZnO–B2 O3 –SiO2 (BZBS) glass (5–20 wt%), and the resultant dielectric constant, coefficient of thermal expansion (CTE), and optical reflectance were investigated for the application of the composites to the barrier ribs in plasma display panels. All the investigated fillers were partially dissolved into the glass at the fabrication temperature (575°C), and the residual fillers were aligned along the boundaries of sintered glass frits. By considering all aspects of the properties, the addition of TiO2 fillers of about 10 wt% to BZBS glass was the most desirable of the types of fillers investigated. The addition of TiO2 filler (10 wt%) yielded 61% in optical reflectance, 8.3 × 10−6 K–1 in coefficient of thermal expansion, and 15.5 in dielectric constant, which were properties comparable with the currently used Pb-based barrier ribs. 相似文献
993.
Shen TJ; Ho NT; Zou M; Sun DP; Cottam PF; Simplaceanu V; Tam MF; Bell DA Jr; Ho C 《Protein engineering, design & selection : PEDS》1997,10(9):1085-1097
A hemoglobin expression system in Escherichia coli is described. In order
to produce authentic human hemoglobin, we need to co-express both
methionine aminopeptidase and globin genes under the control of a strong
promoter. We have constructed three plasmids, pHE2, pHE4 and pHE7, for the
expression of human normal adult hemoglobin and a plasmid, pHE9, for the
expression of human fetal hemoglobin, in high yields. The globin genes can
be derived from either synthetic genes or human globin cDNAs. The extra
amino-terminal methionine residues of the expressed globins can be removed
by the co-expressed methionine aminopeptidase. The heme is inserted
correctly into the expressed alpha- globin from our expression plasmids. A
fraction (approximately 25%) of the heme is not inserted correctly into the
expressed beta- or gamma- globin. However, the incorrectly inserted hemes
can be converted into the correct conformation by carrying out a simple
oxidation-reduction process on the purified hemoglobin molecule. We have
investigated the functional properties of the expressed hemoglobins by
measuring their oxygen-binding properties and their structural features by
obtaining their 1H-NMR spectra. Our results show that authentic human
normal adult and fetal hemoglobins can be produced from our expression
plasmids in E. coli and in high yields. Our expression system allows us to
design and to produce any recombinant hemoglobins needed for our research
on the structure-function relationship in hemoglobin.
相似文献
994.
In this work, polyacrylonitrile (PAN) hollow fibers are pretreated with ammonium dibasic phosphate and then further oxidized in air, carbonized in nitrogen, and activated with carbon dioxide. The adsorption properties of the resultant activated carbon hollow fibers (ACHF) prepared in different conditions were studied. The results show that the adsorption properties of ACHF change regularly with preparing conditions of ACHF. The different adsorption ratios to three adsorbates reflect the number of micropores and mesopores in PAN‐based ACHF. Pretreatment with phosphate can increase the number of mesopores. Proper oxidation temperature and time can increase the number of micropores and mesopores. When carbonization temperature is more than 900°C and carbonization time ranges from 50 to 90 min, the number of micropores and mesopores, especially mesopores, greatly increases. Compared with other treatments, activation treatment greatly increases the number of micropores and mesopores, and the dominant pore sizes of mesopores in PAN‐based ACHF are from 2 to 10 nm. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 602–607, 2004 相似文献
995.
Mechanical properties of high-strength concrete after fire 总被引:2,自引:0,他引:2
With compressive strength grade of C40, C60, and C70, respectively, normal-strength concrete (NSC) and high-strength concrete (HSC) were used to investigate compressive strength, splitting tensile strength, and bending strength after high temperature. The oil furnace is used in this study. Its temperature-time curve is close to standard curve, which conforms to Chinese standard GB/T 9978-1999. After being heated to temperatures of 200, 400, 600, 800, and 1000 °C, respectively, the mechanical properties of HSC were tested. The influence of temperature, water content, specimen size, strength grade, and temperature profiles on mechanical properties of HSC are discussed. 相似文献
997.
998.
999.
1000.
Sun Ying-Chieh; Veenstra David L.; Kollman Peter A. 《Protein engineering, design & selection : PEDS》1996,9(3):273-281
Free energy calculations were carried out to determine the relativeunfolding free energy of the Ile96 wild type and Ala96 mutantbarnases. The total calculated free energies suggest that substitutionof Ile96 with Ala destabilizes barnase by 3.9 kcal/mol, whichis in good agreement with the independently determined experimentalvalues of 4.0 and 3.3 kcal/mol and a previous simulation. However,a decomposition of the free energy finds the dominant contributionsto this free energy arising from the noncovalent Interactionsbetween the perturbed group and distant residues of barnasein the sequence and water molecules and only a very small contributionfrom covalent interactions. This is in contrast to the previoussimulation, using the dual topology methodology, which produceda decomposition with an {small tilde}60% free energy contributionfrom changes in covalent interactions. The use of the singletopology employed in the present calculations and the dual topologyemployed in the previous study are analyzed in order to understandthe contrast between the present results and the results ofthe previous study. 相似文献