全文获取类型
收费全文 | 1437篇 |
免费 | 57篇 |
国内免费 | 7篇 |
专业分类
化学 | 899篇 |
晶体学 | 6篇 |
力学 | 62篇 |
数学 | 317篇 |
物理学 | 217篇 |
出版年
2023年 | 12篇 |
2022年 | 41篇 |
2021年 | 46篇 |
2020年 | 52篇 |
2019年 | 21篇 |
2018年 | 30篇 |
2017年 | 22篇 |
2016年 | 68篇 |
2015年 | 60篇 |
2014年 | 78篇 |
2013年 | 83篇 |
2012年 | 95篇 |
2011年 | 118篇 |
2010年 | 81篇 |
2009年 | 63篇 |
2008年 | 95篇 |
2007年 | 87篇 |
2006年 | 61篇 |
2005年 | 58篇 |
2004年 | 52篇 |
2003年 | 40篇 |
2002年 | 33篇 |
2001年 | 20篇 |
2000年 | 12篇 |
1999年 | 12篇 |
1998年 | 9篇 |
1997年 | 14篇 |
1996年 | 15篇 |
1995年 | 7篇 |
1994年 | 9篇 |
1993年 | 10篇 |
1992年 | 6篇 |
1991年 | 10篇 |
1990年 | 6篇 |
1989年 | 6篇 |
1988年 | 11篇 |
1987年 | 6篇 |
1986年 | 8篇 |
1985年 | 12篇 |
1984年 | 7篇 |
1983年 | 8篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1972年 | 1篇 |
1964年 | 1篇 |
1916年 | 1篇 |
1914年 | 1篇 |
1899年 | 1篇 |
排序方式: 共有1501条查询结果,搜索用时 15 毫秒
31.
Rafael L. C. Jesus Isnar L. P. Silva Fênix A. Araújo Raiana A. Moraes Liliane B. Silva Daniele S. Brito Gabriela B. C. Lima Quiara L. Alves Darizy F. Silva 《Molecules (Basel, Switzerland)》2022,27(21)
Cardiovascular diseases (CVD) are the deadliest noncommunicable disease worldwide. Hypertension is the most prevalent risk factor for the development of CVD. Although there is a wide range of antihypertensive drugs, there still remains a lack of blood pressure control options for hypertensive patients. Additionally, natural products remain crucial to the design of new drugs. The natural product 7-hydroxycoumarin (7-HC) exhibits pharmacological properties linked to antihypertensive mechanisms of action. This study aimed to evaluate the vascular effects of 7-HC in an experimental model of essential hypertension. The isometric tension measurements assessed the relaxant effect induced by 7-HC (0.001 μM–300 μM) in superior mesenteric arteries isolated from hypertensive rats (SHR, 200–300 g). Our results suggest that the relaxant effect induced by 7-HC rely on K+-channels (KATP, BKCa, and, to a lesser extent, Kv) activation and also on Ca2+ influx from sarcolemma and sarcoplasmic reticulum mobilization (inositol 1,4,5-triphosphate (IP3) and ryanodine receptors). Moreover, 7-HC diminishes the mesenteric artery’s responsiveness to α1-adrenergic agonist challenge and improves the actions of the muscarinic agonist and NO donor. The present work demonstrated that the relaxant mechanism of 7-HC in SHR involves endothelium-independent vasorelaxant factors. Additionally, 7-HC reduced vasoconstriction of the sympathetic agonist while improving vascular endothelium-dependent and independent relaxation. 相似文献
32.
Elisabetta Marini Marco Marino Giulia Gionfriddo Federica Maione Marta Pandini Daniele Oddo Marta Giorgis Barbara Rolando Federica Blua Simone Gastaldi Serena Marchi Sandra Kovachka Francesca Spyrakis Eleonora Gianquinto Federica Di Nicolantonio Massimo Bertinaria 《Molecules (Basel, Switzerland)》2022,27(23)
BRAF is a serine/threonine kinase frequently mutated in human cancers. BRAFV600E mutated protein is targeted through the use of kinase inhibitors which are approved for the treatment of melanoma; however, their long-term efficacy is hampered by resistance mechanisms. The PROTAC-induced degradation of BRAFV600E has been proposed as an alternative strategy to avoid the onset of resistance. In this study, we designed a series of compounds where the BRAF kinase inhibitor encorafenib was conjugated to pomalidomide through different linkers. The synthesized compounds maintained their ability to inhibit the kinase activity of mutated BRAF with IC50 values in the 40–88 nM range. Selected compounds inhibited BRAFV600E signaling and cellular proliferation of A375 and Colo205 tumor cell lines. Compounds 10 and 11, the most active of the series, were not able to induce degradation of mutated BRAF. Docking and molecular dynamic studies, conducted in comparison with the efficient BRAF degrader P5B, suggest that a different orientation of the linker bearing the pomalidomide substructure, together with a decreased mobility of the solvent-exposed part of the conjugates, could explain this behavior. 相似文献
33.
Martina Bortolami Paola Di Matteo Daniele Rocco Marta Feroci Rita Petrucci 《Molecules (Basel, Switzerland)》2022,27(15)
Agropyron repens (L.) P. Beauv. (couch grass) is a world-wide infesting rhizomatous plant with pharmacological applications. Chemical research is focused on its allelopathic and anti-inflammatory components, which are mainly present in the essential oil. Conversely, the aqueous extracts have been sparingly investigated, although the herbal tea is by far the most used formulation. To fill the gap, the metabolic profile of Agropyron repens rhizome herbal tea was investigated by electrospray ionization (ESI) tandem–mass spectrometry (MS/MS); the phenolic profile was investigated by HPLC-PDA-ESI-MS/MS. ESI-MS fingerprinting was provided, evidencing diagnostic ions for saccharides, organic acids and amino acids. The HPLC-PDA-ESI-MS/MS analysis evidenced at least 20 characteristic phenolic compounds, the most representative being caffeoyl and feruloyl quinic esters, followed by coumaric, caffeic and ferulic acids, and hesperidin among flavonoids. In addition, the essential amino acid tryptophan was identified for the first time. The results suggest new perspectives of applications for Agropyron repens rhizome. 相似文献
34.
Eleonora Colombo Davide Andrea Coppini Laura Polito Umberto Ciriello Giuseppe Paladino Mariafrancesca Hyeraci Maria Luisa Di Paolo Giulia Nordio Lisa Dalla Via Daniele Passarella 《Molecules (Basel, Switzerland)》2023,28(1)
Cannabidiol (CBD) is a biologically active compound present in the plants of the Cannabis family, used as anticonvulsant, anti-inflammatory, anti-anxiety, and more recently, anticancer drug. In this work, its use as a new self-assembly inducer in the formation of nanoparticles is validated. The target conjugates are characterized by the presence of different anticancer drugs (namely N-desacetyl thiocolchicine, podophyllotoxin, and paclitaxel) connected to CBD through a linker able to improve drug release. These nanoparticles are formed via solvent displacement method, resulting in monodisperse and stable structures having hydrodynamic diameters ranging from 160 to 400 nm. Their biological activity is evaluated on three human tumor cell lines (MSTO-211H, HT-29, and HepG2), obtaining GI50 values in the low micromolar range. Further biological assays were carried out on MSTO-211H cells for the most effective NP 8B, confirming the involvement of paclitaxel in cytotoxicity and cell death mechanism 相似文献
35.
Maria De Fenza Anna Esposito Daniele DAlonzo Annalisa Guaragna 《Molecules (Basel, Switzerland)》2021,26(6)
The de novo synthesis of piperidine nucleosides from our homologating agent 5,6-dihydro-1,4-dithiin is herein reported. The structure and conformation of nucleosides were conceived to faithfully resemble the well-known nucleoside drugs Immucillins H and A in their bioactive conformation. NMR analysis of the synthesized compounds confirmed that they adopt an iminosugar conformation bearing the nucleobases and the hydroxyl groups in the appropriate orientation. 相似文献
36.
Ersilia Nigro Marialuisa Formato Giuseppina Crescente Aurora Daniele 《Molecules (Basel, Switzerland)》2021,26(9)
Cannabis sativa L. is a source of over 150 active compounds known as phytocannabinoids that are receiving renewed interest due to their diverse pharmacologic activities. Indeed, phytocannabinoids mimic the endogenous bioactive endocannabinoids effects through activation of CB1 and CB2 receptors widely described in the central nervous system and peripheral tissues. All phytocannabinoids have been studied for their protective actions towards different biological mechanisms, including inflammation, immune response, oxidative stress that, altogether, result in an inhibitory activity against the carcinogenesis. The role of the endocannabinoid system is not yet completely clear in cancer, but several studies indicate that cannabinoid receptors and endogenous ligands are overexpressed in different tumor tissues. Recently, in vitro and in vivo evidence support the effectiveness of phytocannabinoids against various cancer types, in terms of proliferation, metastasis, and angiogenesis, actions partially due to their ability to regulate signaling pathways critical for cell growth and survival. The aim of this review was to report the current knowledge about the action of phytocannabinoids from Cannabis sativa L. against cancer initiation and progression with a specific regard to brain, breast, colorectal, and lung cancer as well as their possible use in the therapies. We will also report the known molecular mechanisms responsible for such positive effects. Finally, we will describe the actual therapeutic options for Cannabis sativa L. and the ongoing clinical trials. 相似文献
37.
Poly(3,4‐ethylenedioxythiophene):GlycosAminoGlycan Aqueous Dispersions: Toward Electrically Conductive Bioactive Materials for Neural Interfaces 下载免费PDF全文
Daniele Mantione Isabel del Agua Wandert Schaafsma Javier Diez‐Garcia Begona Castro Haritz Sardon David Mecerreyes 《Macromolecular bioscience》2016,16(8):1227-1238
There is an actual need of advanced materials for the emerging field of bioelectronics. One commonly used material is the conducting polymer poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) due to its general use in organic electronics. However, depending on the application in bioelectronics, PEDOT:PSS is not fully biocompatible due to the high acidity of the residual sulfonate protons of PSS. In this paper, the synthesis and biocompatibility properties of new poly(3,4‐ethylenedioxythiophene):GlycosAminoGlycan (PEDOT:GAG) aqueous dispersions and its resulting films are shown. Thus, negatively charged GAGs as an alternative to PSS are presented. Three different commercially available GAGs, hyaluronic acid, heparin, and chondroitin sulfate are used. Indeed, PEDOT:GAGs dispersions are prepared through an oxidative chemical polymerization in water. Biocompatibility assays of the PEDOT:GAGs coatings are performed using SH‐SY5Y and CCF‐STTG1 cell lines and with ATP and Ca2+. Results show full biocompatibility and a pronounced anti‐inflammatory effect. This last characteristic becomes crucial if implanted in the body. These materials can be used for in vivo applications, as transistor or electrode for electrical recording and for all the possible situations when there is contact between electronic circuits and living tissues.
38.
39.
40.