全文获取类型
| 收费全文 | 6177篇 |
| 免费 | 86篇 |
| 国内免费 | 44篇 |
专业分类
| 化学 | 4321篇 |
| 晶体学 | 58篇 |
| 力学 | 104篇 |
| 综合类 | 1篇 |
| 数学 | 954篇 |
| 物理学 | 869篇 |
出版年
| 2024年 | 16篇 |
| 2023年 | 63篇 |
| 2022年 | 105篇 |
| 2021年 | 139篇 |
| 2020年 | 184篇 |
| 2019年 | 169篇 |
| 2018年 | 121篇 |
| 2017年 | 98篇 |
| 2016年 | 191篇 |
| 2015年 | 172篇 |
| 2014年 | 214篇 |
| 2013年 | 293篇 |
| 2012年 | 457篇 |
| 2011年 | 491篇 |
| 2010年 | 237篇 |
| 2009年 | 177篇 |
| 2008年 | 414篇 |
| 2007年 | 382篇 |
| 2006年 | 384篇 |
| 2005年 | 343篇 |
| 2004年 | 317篇 |
| 2003年 | 243篇 |
| 2002年 | 209篇 |
| 2001年 | 88篇 |
| 2000年 | 42篇 |
| 1999年 | 41篇 |
| 1998年 | 39篇 |
| 1997年 | 47篇 |
| 1996年 | 47篇 |
| 1995年 | 36篇 |
| 1994年 | 37篇 |
| 1993年 | 40篇 |
| 1992年 | 33篇 |
| 1991年 | 36篇 |
| 1990年 | 24篇 |
| 1989年 | 19篇 |
| 1988年 | 21篇 |
| 1987年 | 26篇 |
| 1986年 | 25篇 |
| 1985年 | 26篇 |
| 1984年 | 21篇 |
| 1983年 | 21篇 |
| 1982年 | 18篇 |
| 1981年 | 27篇 |
| 1980年 | 23篇 |
| 1979年 | 24篇 |
| 1978年 | 21篇 |
| 1976年 | 15篇 |
| 1975年 | 14篇 |
| 1974年 | 18篇 |
排序方式： 共有6307条查询结果，搜索用时 15 毫秒
31.
The preparation of several 4-heterosubstituted quinuclidines and the pKa values of their hydroperchlorates in water are reported. 相似文献
32.
Dr. Chen-Ming Lin Maritess Arancillo Jonathan Whisenant Prof. Kevin Burgess 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(24):9484-9488
Secondary structures tend to be recognizable because they have repeating structural motifs, but mimicry of these does not have to follow such well-defined patterns. Bioinformatics studies to match side-chain orientations of a novel hydantoin triazole chemotype ( 1 ) to protein-protein interfaces revealed it tends to align well across parallel and antiparallel sheets, like rungs on a ladder. One set of these overlays was observed for the protein-protein interaction uPA⋅uPAR. Consequently, chemotype 1 was made with appropriate side-chains to mimic uPA at this interface. Biophysical assays indicate these compounds did in fact bind uPAR, and elicit cellular responses that affected invasion, migration, and wound healing. 相似文献
33.
Willem Jespers Dr. Grégory Verdon Dr. Jhonny Azuaje Dr. Maria Majellaro Dr. Henrik Keränen Prof. Xerardo García-Mera Dr. Miles Congreve Dr. Francesca Deflorian Dr. Chris de Graaf Dr. Andrei Zhukov Dr. Andrew S. Doré Dr. Jonathan S. Mason Prof. Johan Åqvist Dr. Robert M. Cooke Prof. Eddy Sotelo Dr. Hugo Gutiérrez-de-Terán 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(38):16679-16686
We present a robust protocol based on iterations of free energy perturbation (FEP) calculations, chemical synthesis, biophysical mapping and X-ray crystallography to reveal the binding mode of an antagonist series to the A2A adenosine receptor (AR). Eight A2AAR binding site mutations from biophysical mapping experiments were initially analyzed with sidechain FEP simulations, performed on alternate binding modes. The results distinctively supported one binding mode, which was subsequently used to design new chromone derivatives. Their affinities for the A2AAR were experimentally determined and investigated through a cycle of ligand-FEP calculations, validating the binding orientation of the different chemical substituents proposed. Subsequent X-ray crystallography of the A2AAR with a low and a high affinity chromone derivative confirmed the predicted binding orientation. The new molecules and structures here reported were driven by free energy calculations, and provide new insights on antagonist binding to the A2AAR, an emerging target in immuno-oncology. 相似文献
34.
Dr. Jonathan A. Robson Dr. Markéta Kubánková Tamzin Bond Rian A. Hendley Dr. Andrew J. P. White Prof. Dr. Marina K. Kuimova Prof. Dr. James D. E. T. Wilton-Ely 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(48):21615-21619
A new family of robust, non-toxic, water-compatible ruthenium(II) vinyl probes allows the rapid, selective and sensitive detection of endogenous carbon monoxide (CO) in live mammalian cells under normoxic and hypoxic conditions. Uniquely, these probes incorporate a viscosity-sensitive BODIPY fluorophore that allows the measurement of microscopic viscosity in live cells via fluorescence lifetime imaging microscopy (FLIM) while also monitoring CO levels. This is the first example of a probe that can simultaneously detect CO alongside small viscosity changes in organelles of live cells. 相似文献
35.
Adam D. Martin Jonathan P. Wojciechowski Eric Y. Du Aditya Rawal Holly Stefen Carol G. Au Liming Hou Charles G. Cranfield Thomas Fath Lars M. Ittner Pall Thordarson 《Chemical science》2020,11(5):1375
Peptide-based nanofibres are a versatile class of tunable materials with applications in optoelectronics, sensing and tissue engineering. However, the understanding of the nanofibre surface at the molecular level is limited. Here, a series of homologous dilysine–diphenylalnine tetrapeptides were synthesised and shown to self-assemble into water-soluble nanofibres. Despite the peptide nanofibres displaying similar morphologies, as evaluated through atomic force microscopy and neutron scattering, significant differences were observed in their ability to support sensitive primary neurons. Contact angle and labelling experiments revealed that differential presentation of lysine moieties at the fibre surface did not affect neuronal viability; however the mobility of phenylalanine residues at the nanofibre surface, elucidated through solid- and gel-state NMR studies and confirmed through tethered bilayer lipid membrane experiments, was found to be the determining factor in governing the suitability of a given peptide as a scaffold for primary neurons. This work offers new insights into characterising and controlling the nanofibre surface at the molecular level.The mobility of hydrophobic moieties at a peptide nanofibre surface determines its suitability as a scaffold for sensitive primary cells. 相似文献
36.
Hau Sun Sam Chan Amber L. Thompson Kirsten E. Christensen Jonathan W. Burton 《Chemical science》2020,11(42):11592
Laurefurenynes C–F are four natural products isolated from Laurencia species whose structures were originally determined on the basis of extensive nuclear magnetic resonance experiments. On the basis of a proposed biogenesis, involving a tricyclic oxonium ion as a key intermediate, we have reassigned the structures of these four natural products and synthesized the four reassigned structures using a biomimetic approach demonstrating that they are the actual structures of the natural products. In addition, we have developed a synthesis of the enantiomers of the natural products laurencin and deacetyllaurencin from the enantiomer of (E)-laurefucin using an unusual retrobiomimetic strategy. All of these syntheses have been enabled by the use of tricyclic oxonium ions as pivotal synthetic intermediates.The synthesis and structural reassignment of laurefurenynes C–F has been achieved, with the new structures fitting with a proposed biosynthesis. Also reported is the synthesis of ent-laurencin and ent-deacetyllaurencin via a retrobiomimetic approach. 相似文献
37.
Ganesh K. Mothukuri Sangram S. Kale Carl L. Stenbratt Alessandro Zorzi Jonathan Vesin Julien Bortoli Chapalay Kaycie Deyle Gerardo Turcatti Laura Cendron Alessandro Angelini Christian Heinis 《Chemical science》2020,11(30):7858
Macrocycles provide an attractive modality for drug development, but generating ligands for new targets is hampered by the limited availability of large macrocycle libraries. We have established a solution-phase macrocycle synthesis strategy in which three building blocks are coupled sequentially in efficient alkylation reactions that eliminate the need for product purification. We demonstrate the power of the approach by combinatorially reacting 15 bromoacetamide-activated tripeptides, 42 amines, and 6 bis-electrophile cyclization linkers to generate a 3780-compound library with minimal effort. Screening against thrombin yielded a potent and selective inhibitor (Ki = 4.2 ± 0.8 nM) that efficiently blocked blood coagulation in human plasma. Structure–activity relationship and X-ray crystallography analysis revealed that two of the three building blocks acted synergistically and underscored the importance of combinatorial screening in macrocycle development. The three-component library synthesis approach is general and offers a promising avenue to generate macrocycle ligands to other targets.Combination of three efficient chemical reactions allows for solution-phase synthesis of 3780 macrocycles and identification of potent thrombin inhibitor. 相似文献
38.
Jonathan V. Caspar B.Patrick Sullivan Edward M. Kober Thomas J. Meyer 《Chemical physics letters》1982,91(2):91-95
Values of non-radiative decay rate constants (knr) and emission energies (Ecm) have been obtained for Os(Phen3)2+ in a series of solvents and the results are consistent with the energy gap law. For hydroxylic solvents like water or methanol related studies suggest the existence of strong, specific contributions to the vibrational trapping energy of the solvent. 相似文献
39.
40.
A crude preparation of Aspergillus niger β-glucosidase (27.5 cello-biase U/mg protein at 40°C, pH 5.0) was immobilized on
concanavalin A-Sepharose (CAS). The cellobiase activity of the immobilized enzyme was 1334 U/mg dried CAS or 108 U/mL CAS
gel. The β-glucosidase-CAS complex was entrapped within crosslinked propylene glycol alginate/bone-geletin gel spheres that
possessed between 0.67 and 2.35 cellobiase U/mL spheres, depending on their size. The effect of cellobiose concentration (10–300
mM) on the activity of native, immobilized, and gel-entrapped enzyme was determined. It was shown that concentrations of cellobiose
between 10 and 180 mM were not inhibitory to the entrapped enzyme, although inhibition was found to occur with the native
and immobilized enzyme. Exogenous ion addition was not necessary to maintain the structural integrity of the spheres, which
were stable for 4 d at 40°C. 相似文献