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991.
Medicinal chemistry is facing new challenges in approaching precision medicine. Several powerful new tools or improvements of already used tools are now available to medicinal chemists to help in the process of drug discovery, from a hit molecule to a clinically used drug. Among the new tools, the possibility of considering folding intermediates or the catalytic process of a protein as a target for discovering new hits has emerged. In addition, machine learning is a new valuable approach helping medicinal chemists to discover new hits. Other abilities, ranging from the better understanding of the time evolution of biochemical processes to the comprehension of the biological meaning of the data originated from genetic analyses, are on their way to progress further in the drug discovery field toward improved patient care. In this sense, the new approaches to the delivery of drugs targeted to the central nervous system, together with the advancements in understanding the metabolic pathways for a growing number of drugs and relating them to the genetic characteristics of patients, constitute important progress in the field. 相似文献
992.
993.
The aim of this paper is the presentation of new models for option pricing that are discrete in time and in the framework of Markov and semi-Markov processes as an alternative to the classical Cox–Rubinstein model, and that also allow the possibility of arbitrage. Both cases of European and American options are considered and possible extensions are given. © 1997 by John Wiley & Sons, Ltd. 相似文献
994.
Marco Garzotti Luca Rovatti Mahmoud Hamdan 《Rapid communications in mass spectrometry : RCM》1998,12(8):484-488
Adduction between acrylamide and cysteine residues is a post-translational modification associated with proteins separated by gel electrophoresis. In the present article, three model peptides containing 2–4 cysteine residues were reduced with dithiothreitol, incubated with acrylamide monomers and examined by on-line liquid chromatography coupled to electrospray tandem mass spectrometry. Each of the solutions examined in this work revealed the presence of four distinct components: the free peptide, two different peptide–acrylamide 1:1 adducts involving two cysteine residues at different positions within the same sequence, and peptide–acrylamide 1:2 adducts. The use of liquid chromatography allowed the separation of components which differed only by the site of complexation of acrylamide, while the application of tandem mass spectrometry furnished reliable sequencing information permitting the identification of most cysteine residues involved in such complexation. © 1998 John Wiley & Sons, Ltd. 相似文献
995.
Masumi Asakawa Peter R. Ashton Vincenzo Balzani Alberto Credi Christoph Hamers Gunter Mattersteig Marco Montalti Andrew N. Shipway Neil Spencer J. Fraser Stoddart Malcolm S. Tolley Margherita Venturi Andrew J. P. White David J. Williams 《Angewandte Chemie (International ed. in English)》1998,37(3):333-337
A mechanical switch in a [2]catenane , made up of a cyclobis(paraquat-p-phenylene) tetracation interlocked with a macrocyclic polyether containing a redox-active tetrathiafulvalene (TTF) unit and a 1,5-dioxynaphthalene ring system, can be thrown either chemically or electrochemically. The neutral TTF unit resides “inside” the tetracationic cyclophane in the reduced state and “alongside” it in the oxidized species (TTF+/ TTF2+). Switching between the reduced (I4+) and oxidized state (I5+(I6+)) is accompanied by a dramatic color change. 相似文献
996.
Marco Buratti 《组合设计杂志》1998,6(3):165-182
We present a new recursive construction for difference matrices whose application allows us to improve some results by D. Jungnickel. For instance, we prove that for any Abelian p-group G of type (n1, n2, …, nt) there exists a (G, pe, 1) difference matrix with e = Also, we prove that for any group G there exists a (G, p, 1) difference matrix where p is the smallest prime dividing |G|. Difference matrices are then used for constructing, recursively, relative difference families. We revisit some constructions by M. J. Colbourn, C. J. Colbourn, D. Jungnickel, K. T. Phelps, and R. M. Wilson. Combining them we get, in particular, the existence of a multiplier (G, k, λ)-DF for any Abelian group G of nonsquare-free order, whenever there exists a (p, k, λ)-DF for each prime p dividing |G|. Then we focus our attention on a recent construction by M. Jimbo. We improve this construction and prove, as a corollary, the existence of a (G, k, λ)-DF for any group G under the same conditions as above. © 1998 John Wiley & Sons, Inc. J Combin Designs 6: 165–182, 1998 相似文献
997.
998.
Wei Cao Jianfeng Jin Gang Wu Nathalie Bravenboer Marco N. Helder Janak L. Pathak Behrouz Zandieh-Doulabi Jolanda M. A. Hogervorst Shingo Matsukawa Lester C. Geonzon Rommel G. Bacabac Engelbert A. J. M. Schulten Jenneke Klein-Nulend 《Molecules (Basel, Switzerland)》2021,26(20)
Current cell-based bone tissue regeneration strategies cannot cover large bone defects. K-carrageenan is a highly hydrophilic and biocompatible seaweed-derived sulfated polysaccharide, that has been proposed as a promising candidate for tissue engineering applications. Whether κ-carrageenan can be used to enhance bone regeneration is still unclear. In this study, we aimed to investigate whether κ-carrageenan has osteogenic potential by testing its effect on pre-osteoblast proliferation and osteogenic differentiation in vitro. Treatment with κ-carrageenan (0.5 and 2 mg/mL) increased both MC3T3-E1 pre-osteoblast adhesion and spreading at 1 h. K-carrageenan (0.125–2 mg/mL) dose-dependently increased pre-osteoblast proliferation and metabolic activity, with a maximum effect at 2 mg/mL at day three. K-carrageenan (0.5 and 2 mg/mL) increased osteogenic differentiation, as shown by enhanced alkaline phosphatase activity (1.8-fold increase at 2 mg/mL) at day four, and matrix mineralization (6.2-fold increase at 2 mg/mL) at day 21. K-carrageenan enhanced osteogenic gene expression (Opn, Dmp1, and Mepe) at day 14 and 21. In conclusion, κ-carrageenan promoted MC3T3-E1 pre-osteoblast adhesion and spreading, metabolic activity, proliferation, and osteogenic differentiation, suggesting that κ-carrageenan is a potential osteogenic inductive factor for clinical application to enhance bone regeneration. 相似文献
999.