全文获取类型
收费全文 | 2140篇 |
免费 | 241篇 |
国内免费 | 1篇 |
专业分类
电工技术 | 8篇 |
综合类 | 3篇 |
化学工业 | 691篇 |
金属工艺 | 26篇 |
机械仪表 | 20篇 |
建筑科学 | 93篇 |
矿业工程 | 77篇 |
能源动力 | 32篇 |
轻工业 | 451篇 |
水利工程 | 20篇 |
石油天然气 | 6篇 |
无线电 | 132篇 |
一般工业技术 | 328篇 |
冶金工业 | 261篇 |
原子能技术 | 13篇 |
自动化技术 | 221篇 |
出版年
2023年 | 33篇 |
2022年 | 65篇 |
2021年 | 93篇 |
2020年 | 56篇 |
2019年 | 53篇 |
2018年 | 62篇 |
2017年 | 92篇 |
2016年 | 119篇 |
2015年 | 102篇 |
2014年 | 104篇 |
2013年 | 185篇 |
2012年 | 128篇 |
2011年 | 137篇 |
2010年 | 120篇 |
2009年 | 96篇 |
2008年 | 117篇 |
2007年 | 117篇 |
2006年 | 74篇 |
2005年 | 68篇 |
2004年 | 61篇 |
2003年 | 48篇 |
2002年 | 53篇 |
2001年 | 41篇 |
2000年 | 32篇 |
1999年 | 28篇 |
1998年 | 38篇 |
1997年 | 40篇 |
1996年 | 17篇 |
1995年 | 22篇 |
1994年 | 24篇 |
1993年 | 17篇 |
1992年 | 11篇 |
1991年 | 7篇 |
1990年 | 7篇 |
1989年 | 4篇 |
1988年 | 14篇 |
1987年 | 11篇 |
1986年 | 5篇 |
1985年 | 4篇 |
1984年 | 9篇 |
1983年 | 11篇 |
1982年 | 8篇 |
1981年 | 6篇 |
1980年 | 5篇 |
1979年 | 8篇 |
1977年 | 5篇 |
1975年 | 6篇 |
1970年 | 3篇 |
1969年 | 2篇 |
1968年 | 2篇 |
排序方式: 共有2382条查询结果,搜索用时 187 毫秒
91.
Rafaela Gladysz Prof. Dr. Anne‐Marie Lambeir Dr. Jurgen Joossens Prof. Dr. Koen Augustyns Prof. Dr. Pieter Van der Veken 《ChemMedChem》2016,11(5):467-476
Substrate activity screening (SAS) was presented a decade ago by Ellman and co‐workers as a straightforward methodology for the identification of fragment‐sized building blocks for enzyme inhibitors. Ever since, SAS and variations derived from it have been successfully applied to the discovery of inhibitors of various families of enzymatically active drug targets. This review covers key achievements and challenges of SAS and related methodologies, including the modified substrate activity screening (MSAS) approach. Special attention is given to the kinetic and thermodynamic aspects of these methodologies, as a thorough understanding thereof is crucial for successfully transforming the identified fragment‐sized hits into potent inhibitors. 相似文献
92.
Structure–Activity Relationships of JMV4463, a Vectorized Cathepsin D Inhibitor with Antiproliferative Properties: The Unique Role of the AMPA‐Based Vector
下载免费PDF全文
![点击此处可从《ChemMedChem》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Dr. Lubomir L. Vezenkov Clément A. Sanchez Dr. Virginie Bellet Dr. Vincent Martin Dr. Marie Maynadier Dr. Nadir Bettache Prof. Vincent Lisowski Prof. Jean Martinez Dr. Marcel Garcia Dr. Muriel Amblard Dr. Jean‐François Hernandez 《ChemMedChem》2016,11(3):302-308
Cathepsin D (CathD) is overexpressed and secreted by several solid tumors and stimulates their growth, the mechanism of which is still not understood. In this context, the pepstatin bioconjugate JMV4463 [Ac‐arg‐O2Oc‐(Val)3‐Sta‐Ala‐Sta‐(AMPA)4‐NH2; O2Oc=8‐amino‐3,6‐dioxaoctanoyl, Sta=statine, AMPA=ortho‐aminomethylphenylacetyl], containing a new kind of cell‐penetrating vector, was previously shown to exhibit potent antiproliferative effects in vitro and to delay the onset of tumors in vivo. In this study, we performed a structure–activity relationship analysis to evaluate the significance of the inhibitor and vector moieties of JMV4463. By modifying both statine residues of pepstatin we found that the antiproliferative activity is correlated with CathD inhibition, supporting a major role of the catalytic activity of intracellular CathD in cancer cell proliferation. Replacing the vector composed of four AMPA units with other vectors was found to abolish cytotoxicity, although all of the conjugates enabled pepstatin transport into cells. In addition, the AMPA4 vector must be localized at the C terminus of the bioconjugate. The unexpected importance of the vector structure and position for cytotoxic action suggests that AMPA4 enables pepstatin to inhibit the proteolysis of critical CathD substrates involved in cell proliferation via a unique mechanism of action. 相似文献
93.
Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors
下载免费PDF全文
![点击此处可从《ChemMedChem》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Dr. Gordon J. Florence Andrew L. Fraser Dr. Eoin R. Gould Elizabeth F. King Stefanie K. Menzies Dr. Joanne C. Morris Marie I. Thomson Dr. Lindsay B. Tulloch Marija K. Zacharova Prof. Dr. Terry K. Smith 《ChemMedChem》2016,11(14):1503-1506
Neglected tropical diseases caused by parasitic infections are an ongoing and increasing concern. They are a burden to human and animal health, having the most devastating effect on the world′s poorest countries. Building upon our previously reported triazole analogues, in this study we describe the synthesis and biological testing of other novel heterocyclic acetogenin‐inspired derivatives, namely 3,5‐isoxazoles, furoxans, and furazans. Several of these compounds maintain low‐micromolar levels of inhibition against Trypanosoma brucei, whilst having no observable inhibitory effect on mammalian cells, leading to the possibility of novel lead compounds for selective treatment. 相似文献
94.
Dr. Tessa Lühmann Valerie Spieler Dr. Vera Werner Dr. Marie‐Gabrielle Ludwig Dr. Juliane Fiebig Prof. Dr. Thomas D. Mueller Prof. Dr. Dr. Lorenz Meinel 《Chembiochem : a European journal of chemical biology》2016,17(22):2123-2128
Driving macrophage (M?) polarization into the M2 phenotype provides potential against inflammatory diseases. Interleukin‐4 (IL‐4) promotes polarization into the M2‐M? phenotype, but its systemic use is constrained by dose‐limiting toxicity. Consequently, we developed IL‐4‐decorated surfaces aiming at sustained and localized activity. IL‐4 muteins were generated by genetic code expansion; Lys42 was replaced by unnatural amino acids (uAAs). Both muteins showed cell‐stimulation ability and binding affinity to IL4Rα similar to those of wt‐IL‐4. Copper‐catalyzed (CuAAC) and copper‐free strain‐promoted (SPAAC) 1,3‐dipolar azide–alkyne cycloadditions were used to site‐selectively anchor IL‐4 to agarose surfaces. These surfaces had sustained IL‐4 activity, as demonstrated by TF‐1 cell proliferation and M2, but not M1, polarization of M‐CSF‐generated human M?. The approach provides a blueprint for the engineering of cytokine‐activated surfaces profiled for sustained and spatially controlled activity. 相似文献
95.
Dr. Marie Monestier Peggy Charbonnier Dr. Christelle Gateau Dr. Martine Cuillel Faustine Robert Colette Lebrun Dr. Elisabeth Mintz Prof. Olivier Renaudet Dr. Pascale Delangle 《Chembiochem : a European journal of chemical biology》2016,17(7):590-594
Liver cells are an essential target for drug delivery in many diseases. The hepatocytes express the asialoglycoprotein receptor (ASGPR), which promotes specific uptake by means of N‐acetylgalactosamine (GalNAc) recognition. In this work, we designed two different chemical architectures to treat Wilson's disease by intracellular copper chelation. Two glycoconjugates functionalized with three or four GalNAc units each were shown to enter hepatic cells and chelate copper. Here, we studied two series of compounds derived from these glycoconjugates to find key parameters for the targeting of human hepatocytes. Efficient cellular uptake was demonstrated by flow cytometry using HepG2 human heptic cells that express the human oligomeric ASGPR. Dissociation constants in the nanomolar range showed efficient multivalent interactions with the receptor. Both architectures were therefore concluded to be able to compete with endogeneous asialoglycoproteins and serve as good vehicles for drug delivery in hepatocytes. 相似文献
96.
97.
This paper introduces a new methodology to measure the elastic constants of transversely isotropic rocks from a single uniaxial compression test. We first give the mathematical proof that a uniaxial compression test provides only four independent strain equations. As a result, the exact determination of all five independent elastic constants from only one test is not possible. An approximate determination of the Young's moduli and the Poisson's ratios is however practical and efficient when adding the Saint–Venant relation as the fifth equation. Explicit formulae are then developed to calculate both secant and tangent definitions of the five elastic constants from a minimum of four strain measurements. The results of this new methodology applied on three granitic samples demonstrate a significant stress-induced nonlinear behavior, where the tangent moduli increase by a factor of three to four when the rock is loaded up to 20 MPa. The static elastic constants obtained from the uniaxial compression test are also found to be significantly smaller than the dynamic ones obtained from the ultrasonic measurements. 相似文献
98.
Rakhi Sood Mona Marie Obadia Bhanu Prakash Mudraboyina Biao Zhang Anatoli Serghei Julien Bernard Eric Drockenmuller 《Polymer》2014
Nitroxide-mediated radical polymerization of a tailor-made acrylate carrying a 1,2,3-triazole group with an undecanoyl spacer affords a well-defined (Mn = 7860 g mol−1 and D = 1.39) neutral polyacrylate precursor. A series of 1,2,3-triazolium-based poly(ionic liquid)s (TPILs) is then obtained by straightforward quaternization of the 1,2,3-triazole groups with methyl iodide and subsequent anion metathesis reactions. Among the prepared materials, TPIL with bis(trifluoromethane)sulfonimide anion exhibits low glass transition temperature (Tg = −40 °C), high thermal stability (Td10 = 325 °C) and anhydrous ionic conductivity of 4 × 10−6 S cm−1 at 30 °C, as measured by differential scanning calorimetry, thermogravimetric analysis and broadband dielectric spectroscopy, respectively. 相似文献
99.
Impact of the Cd2+ treatment on the electrical properties of Cu2ZnSnSe4 and Cu(In,Ga)Se2 solar cells
Khaled Ben Messaoud Marie Buffire Guy Brammertz Hossam ElAnzeery Souhaib Oueslati Jonathan Hamon Bas J. Kniknie Marc Meuris Mosbah Amlouk Jef Poortmans 《Progress in Photovoltaics: Research and Applications》2015,23(11):1608-1620
The present contribution aims at determining the impact of modifying the properties of the absorber/buffer layer interface on the electrical performance of Cu2ZnSnSe4 (CZTSe) thin‐film solar cells, by using a Cd2+ partial electrolyte (Cd PE) treatment of the absorber before the buffer layer deposition. In this work, CZTSe/CdS solar cells with and without Cd PE treatment were compared with their respective Cu(In,Ga)Se2 (CIGSe)/CdS references. The Cd PE treatment was performed in a chemical bath for 7 min at 70 °C using a basic solution of cadmium acetate. X‐ray photoemission spectroscopy measurements have revealed the presence of Cd at the absorber surface after the treatment. The solar cells were characterized using current density–voltage (J–V), external quantum efficiency, and drive‐level capacitance profiling measurements. For the CZTSe‐based devices, the fill factor increased from 57.7% to 64.0% when using the Cd PE treatment, leading to the improvement of the efficiency (η) from 8.3% to 9.0% for the best solar cells. Similar observations were made on the CIGSe solar cell reference. This effect comes from a considerable reduction of the series resistance (RS) of the dark and light J–V, as determined using the one‐diode model. The crossover effect between dark and light J–V curves is also significantly reduced by Cd PE treatment. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
100.
Effects of Aluminium Contamination on the Nervous System of Freshwater Aquatic Vertebrates: A Review
Marie Closset Katia Cailliau Sylvain Slaby Matthieu Marin 《International journal of molecular sciences》2022,23(1)
Aluminium (Al) is the most common natural metallic element in the Earth’s crust. It is released into the environment through natural processes and human activities and accumulates in aquatic environments. This review compiles scientific data on the neurotoxicity of aluminium contamination on the nervous system of aquatic organisms. More precisely, it helps identify biomarkers of aluminium exposure for aquatic environment biomonitoring in freshwater aquatic vertebrates. Al is neurotoxic and accumulates in the nervous system of aquatic vertebrates, which is why it could be responsible for oxidative stress. In addition, it activates and inhibits antioxidant enzymes and leads to changes in acetylcholinesterase activity, neurotransmitter levels, and in the expression of several neural genes and nerve cell components. It also causes histological changes in nerve tissue, modifications of organism behaviour, and cognitive deficit. However, impacts of aluminium exposure on the early stages of aquatic vertebrate development are poorly described. Lastly, this review also poses the question of how accurate aquatic vertebrates (fishes and amphibians) could be used as model organisms to complement biological data relating to the developmental aspect. This “challenge” is very relevant since freshwater pollution with heavy metals has increased in the last few decades. 相似文献