全文获取类型
收费全文 | 13026篇 |
免费 | 872篇 |
国内免费 | 1503篇 |
出版年
2024年 | 80篇 |
2023年 | 247篇 |
2022年 | 317篇 |
2021年 | 352篇 |
2020年 | 437篇 |
2019年 | 564篇 |
2018年 | 482篇 |
2017年 | 380篇 |
2016年 | 358篇 |
2015年 | 404篇 |
2014年 | 886篇 |
2013年 | 1271篇 |
2012年 | 693篇 |
2011年 | 676篇 |
2010年 | 512篇 |
2009年 | 575篇 |
2008年 | 591篇 |
2007年 | 647篇 |
2006年 | 573篇 |
2005年 | 613篇 |
2004年 | 431篇 |
2003年 | 456篇 |
2002年 | 388篇 |
2001年 | 323篇 |
2000年 | 234篇 |
1999年 | 252篇 |
1998年 | 275篇 |
1997年 | 222篇 |
1996年 | 233篇 |
1995年 | 278篇 |
1994年 | 259篇 |
1993年 | 216篇 |
1992年 | 197篇 |
1991年 | 124篇 |
1990年 | 103篇 |
1989年 | 71篇 |
1988年 | 64篇 |
1987年 | 51篇 |
1986年 | 59篇 |
1985年 | 63篇 |
1984年 | 89篇 |
1983年 | 57篇 |
1982年 | 65篇 |
1981年 | 52篇 |
1980年 | 46篇 |
1979年 | 35篇 |
1978年 | 19篇 |
1977年 | 21篇 |
1976年 | 18篇 |
1973年 | 13篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
11.
《基因组蛋白质组与生物信息学报(英文版)》2020,18(2):104-119
To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to generate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000. 相似文献
12.
The collective redox activities of transition‐metal (TM) cations and oxygen anions have been shown to increase charge storage capacity in both Li‐rich layered and cation‐disordered rock‐salt cathodes. Repeated cycling involving anionic redox is known to trigger TM migration and phase transformation in layered Li‐ and Mn‐rich (LMR) oxides, however, detailed mechanistic understanding on the recently discovered Li‐rich rock‐salt cathodes is largely missing. The present study systematically investigates the effect of oxygen redox on a Li1.3Nb0.3Mn0.4O2 cathode and demonstrates that performance deterioration is directly correlated to the extent of oxygen redox. It is shown that voltage fade and hysteresis begin only after initiating anionic redox at high voltages, which grows progressively with either deeper oxidation of oxygen at higher potential or extended cycling. In contrast to what is reported on layered LMR oxides, extensive TM reduction is observed but phase transition is not detected in the cycled oxide. A densification/degradation mechanism is proposed accordingly which elucidates how a unique combination of extensive chemical reduction of TM and reduced quality of the Li percolation network in cation‐disordered rock‐salts can lead to performance degradation in these newer cathodes with 3D Li migration pathways. Design strategies to achieve balanced capacity and stability are also discussed. 相似文献
13.
The reactions of aliphatic and aromatic amines with reducing sugars are important in both drug stability and synthesis. The
formation of glycosylamines in solution, the first step in the Maillard reaction, does not typically cause browning but results
in decreased potency and is hence significant from the aspect of drug instability. The purpose of this research was to present
(1) unreported ionic equilibria of model reactant (kynurenine), (2) the analytical methods used to characterize and measure
reaction products, (3) the kinetic scheme used to measure reaction rates and (4) relevant properties of various reducing sugars
that impact the reaction rate in solution. The methods used to identify the reversible formation of two products from the
reaction of kynurenine and monosaccharides included LC mass spectrometry, UV spectroscopy, and 1-D and 2-D 1H–1H COSY NMR spectroscopy. Kinetics was studied using a stability-indicating HPLC method. The results indicated the formation
of α and β glycosylamines by a pseudo first-order reversible reaction scheme in the pH range of 1–6. The forward reaction
was a function of initial glucose concentration but not the reverse reaction. It was concluded that the reaction kinetics
and equilibrium concentrations of the glycosylamines were pH-dependent and also a function of the acyclic content of the reacting
glucose isomer. 相似文献
14.
A. V. Kireyko I. A. Veselova T. N. Shekhovtsova 《Russian Journal of Bioorganic Chemistry》2006,32(1):71-77
Peroxidase oxidation of o-dianisidine, 3,3′,5,5′-tetramethylbenzidine, and o-phenylenediamine in the presence of sodium dodecyl sulfate (SDS), an anionic surfactant, was spectrophotometrically studied. It was found that 0.1–100 mM SDS concentrations stabilize intermediates formed in the peroxidase oxidation of these substrates. The cause of the stabilization is an electrostatic interaction between positively charged intermediates and negatively charged surfactant. 相似文献
15.
zge Karayel Francesca Tonelli Sebastian Virreira Winter Phillip E. Geyer Ying Fan Esther M. Sammler Dario R. Alessi Martin Steger Matthias Mann 《Molecular & cellular proteomics : MCP》2020,19(9):1546-1560
- Download : Download high-res image (63KB)
- Download : Download full-size image
- •MS-based clinical assay that accurately determines phospho Rab10 occupancy.
- •Stable isotope labeled phosphopeptide injected as a standard with endogenous tryptic phospho Rab peptide for accurate ratio determination.
- •Determination of pRab levels in neutrophils of Parkinson disease patients.
- •Relevance of pRab levels as marker of PD.
16.
《Bioorganic & medicinal chemistry letters》2020,30(16):127289
The present research project details synthesis of new hybrid methanofullerenes based on acetylene and triazole esters of malonic acid containing 5Z,9Z-dienoic acids and fullerene C60 under Bingel-Hirsch conditions, including study of the cytotoxic activity with respect to Jurkat, K562, U937 and HL60 tumor cell lines. Hybrid methanofullerenes containing acetylenic fragments, unlike triazole substituents, were found to exhibit higher cytotoxicity, but are characterized by lower selectivity of action in relation to healthy cells. 相似文献
17.
18.
Algirdas Mikalkėnas Bazilė Ravoitytė Daiva Tauraitė Elena Servienė Rolandas Meškys 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):384-389
Small molecule inhibitors have a powerful blocking action on viral polymerases. The bioavailability of the inhibitor, nevertheless, often raise a significant selectivity constraint and may substantially limit the efficacy of therapy. Phosphonoacetic acid has long been known to possess a restricted potential to block DNA biosynthesis. In order to achieve a better affinity, this compound has been linked with natural nucleotide at different positions. The structural context of the resulted conjugates has been found to be crucial for the acquisition by DNA polymerases. We show that nucleobase-conjugated phosphonoacetic acid is being accepted, but this alters the processivity of DNA polymerases. The data presented here not only provide a mechanistic rationale for a switch in the mode of DNA synthesis, but also highlight the nucleobase-targeted nucleotide functionalization as a route for enhancing the specificity of small molecule inhibitors. 相似文献
19.
20.
《Bioorganic & medicinal chemistry letters》2014,24(8):1980-1982
A convenient synthesis of four new enantiomerically pure acidic amino acids is reported and their affinity at ionotropic glutamate receptors was determined. The new compounds are higher homologues of glutamic acid in which the molecular complexity has been increased by introducing an aromatic/heteroaromatic ring, that is a phenyl or a thiophene ring, that could give additional electronic interactions with the receptors. The results of the present investigation indicate that the insertion of an aromatic/heteroaromatic ring into the amino acid skeleton of glutamate higher homologues is well tolerated and this modification could be exploited to generate a new class of NMDA antagonists. 相似文献