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71.
Methinylogation Approach in Chiral Pharmacophore Design: from Alkynyl‐ to Allenyl‐carbinol Warheads against Tumor Cells
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Dr. Dymytrii Listunov Dr. Etienne Joly Dr. Carine Duhayon Dr. Nathalie Saffon‐Merceron Isabelle Fabing Dr. Yves Génisson Dr. Valérie Maraval Prof. Remi Chauvin 《ChemMedChem》2018,13(16):1711-1722
Extension of a structure–activity relationship study of the antitumor cytotoxicity of lipidic dialkynylcarbinols (DACs) is envisaged by formal methinylogation of one of the ethyndiyl moieties of the DAC warhead into the corresponding allenylalkynylcarbinol (AllAC) counterpart. External AllACs were directly obtained by methinylation of the parent DACs with formaldehyde in either the racemic or scalemic series. Isomers containing external progargyl and propynyl motifs were also prepared. Internal AllACs were obtained as racemic statistical mixtures of stereoisomers in two steps from the key C5‐DAC rac‐TIPS‐C≡C‐CH(OH)‐C≡CH and aldehydes. Kinetic resolution of the (S)‐C5‐DAC in 97 % ee and (R)‐C5‐DAC in 99 % ee was achieved by sequential lipase‐mediated acetylation/hydrolysis using the Candida antartica lipase (Novozyme 435). The four internal AllAC stereoisomers were prepared by asymmetric methinylation with (R)‐ or (S)‐diphenylprolinol as chiral auxiliary. Cytotoxicity assays on HCT116 cancer cells showed that the most active (eutomeric) external or internal AllAC exhibits an S configuration, a fatty chain length of n=12, and a 50 % inhibitory concentration IC50≈1.0 μm . 相似文献
72.
Emmanuel Mornet Nathalie Carmoy Céline Lainé Lo?c Lemiègre Tony Le Gall Isabelle Laurent Remi Marianowski Claude Férec Pierre Lehn Thierry Benvegnu Tristan Montier 《International journal of molecular sciences》2013,14(1):1477-1501
Since recombinant viral vectors have been associated with serious side effects, such as immunogenicity and oncogenicity, synthetic delivery systems represent a realistic alternative for achieving efficacy in gene therapy. A major challenge for non-viral nanocarriers is the optimization of transgene expression in the targeted cells. This goal can be achieved by fine-tuning the chemical carriers and the adding specific motifs to promote cellular penetration. Our study focuses on the development of novel folate-based complexes that contain varying quantities of folate motifs. After controlling for their physical properties, neutral folate-modified lipid formulations were compared in vitro to lipoplexes leading to comparable expression levels. In addition, no cytotoxicity was detected, unlike what was observed in the cationic controls. Mechanistically, the delivery of the transgene appeared to be, in part, due to endocytosis mediated by folate receptor targeting. This mechanism was further validated by the observation that adding free folate into the medium decreased luciferase expression by 50%. In vivo transfection with the folate-modified MM18 lipid, containing the highest amount of FA-PEG570-diether co-lipid (w:w; 90:10), at a neutral charge ratio, gave luciferase transgene expression. These studies indicate that modification of lipids with folate residues could enhance non-toxic, cell-specific gene delivery. 相似文献
73.
Kevin Cronin Muammer Catak Sean Dempsey Remi Ollagnier 《American Institute of Chemical Engineers》2010,56(1):114-124
The sliding conveyor consists of a plane surface, known as the track, along which particles are induced to move by vibrating the bed sinusoidal with respect to time. The forces on the particle include gravity, bed reaction force and friction. Because friction coefficients are inherently variable, particle motion along the bed is erratic and unpredictable. A deterministic model of particle motion (where friction is considered to be known and invariant) is selected and its output validated by experiment. Two probabilistic solution techniques are developed and applied to the deterministic model, in order to account for the randomness that is present. The two methods consider particle displacement to be represented by discrete time and continuous time random processes, respectively, and permits analytical solutions for mean and variance in displacement versus time to be found. These are compared with experimental measurements of particle motion. Ultimately this analysis can be employed to calculate residence‐time distributions for such items of process equipment. © 2009 American Institute of Chemical Engineers AIChE J, 2010 相似文献
74.
Der-Jang Liaw Been-Yang Liaw Bernard Sillion Rgis Mercier Remi Thiria Hikaru Sekiguchi 《Polymer International》1999,48(6):473-478
A series of novel benzhydrol-containing poly(amide-imide)s (PAIs) have been prepared from a new diimide-dicarboxylic acid, N,N′-bis(4-hydroxycarbonyl)-benzhydrol-3,3′,4,4′-tetracarboxydiimide (BHTDA-DIA), with various diamines by direct polycondensation using triphenyl phosphite and pyridine as condensing agents. The polymers obtained had inherent viscosities of 0.35–0.96 dl g−1. All these PAIs, except polymer PAI-2, were soluble in N-methyl-2-pyrrolidinone and N,N-dimethylacetamide containing LiCl (1 wt%). Tough and flexible PAI films could be obtained by casting PAIs from their DMAc or NMP solutions, except for polymer PAI-2. The polymer films had a tensile strength of 93–111 MPa, an elongation at break range of 4–6%, and an initial modulus range of 2.7–3.8 GPa. The glass transition temperatures of most polymers were found to be above 255 °C. These polymers were fairly stable up to a temperature around or above 400 °C, and lost 10% weight in the range 426–507 °C in nitrogen and 423–515 °C in air. © 1999 Society of Chemical Industry 相似文献
75.
Pontikakis George N. Koltsakis Grigorios C. Stamatelos Anastasios M. Noirot Remi Agliany Yvan Colas Henry Versaevel Philippe Bourgeois Christelle 《Topics in Catalysis》2001,16(1-4):329-335
The work presented in this paper was aimed at detecting, understanding and modeling some critical behavior aspects of zeolite-containing diesel catalysts. An already available mathematical model for precious metal catalysts was used as a starting point. A specially designed set of experiments provided the information needed to improve certain modeling features. New submodels were introduced to account for hydrocarbon and H2O adsorption, as well as diffusion limitations in the zeolite. The effect of flow maldistribution during real world operation was investigated experimentally and computationally. Although a number of issues (especially regarding the DeNOx mechanisms) are not yet fully resolved, significant progress was achieved as regards the understanding and computational prediction of diesel catalyst operation. 相似文献
76.
Ge Xiaojia; Conger Rand D.; Cadoret Remi J.; Neiderhiser Jenae M.; Yates William; Troughton Edward; Stewart Mark A. 《Canadian Metallurgical Quarterly》1997,33(1):2
Reports an error in the original article by X. Ge et al (Developmental Psychology, 1996 [Jul], Vol 32[4], 574–589). On page 584, Figure 2, negative signs were mistakenly inserted in front of 2 coefficients. The correct coefficients are given. (The following abstract of this article originally appeared in record 1996-01781-002.). Using an adoption design to collect data on biological and adoptive parents of children adopted at birth, this study explored a possible mechanism through which heritable characteristics of adopted children evoke adoptive parent responses and lead to reciprocal influences between adoptive parent and adopted child behavior. Participants were 25 male and 20 female adoptees, 12–18 years of age, having either a biological parent with substance abuse/dependency or antisocial personality or a biological parent with no such history. The study found that psychiatric disorders of biological parents were significantly related to children's antisocial/hostile behaviors and that biological parents' psychiatric disorders were associated with adoptive parents' behaviors. This genotype-environment association was largely mediated by adoptees' antisocial/hostile behaviors. Results also suggest that the adoptee's antisocial/hostile behavior and adoptive… (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
77.
Ge Xiaojia; Conger Rand D.; Cadoret Remi J.; Neiderhiser Jenae M.; Yates William; Troughton Edward; Stewart Mark A. 《Canadian Metallurgical Quarterly》1996,32(4):574
Using an adoption design to collect data on biological and adoptive parents of children adopted at birth, this study explored a possible mechanism through which heritable characteristics of adopted children evoke adoptive parent responses and lead to reciprocal influences between adoptive parent and adopted child behavior. Participants were 25 male and 20 female adoptees, 12-18 years of age, having either a biological parent with substance abuse/dependency or antisocial personality or a biological parent with no such history. The study found that psychiatric disorders of biological parents were significantly related to children's antisocial/hostile behaviors and that biological parents' psychiatric disorders were associated with adoptive parents' behaviors. This genotype-environment association was largely mediated by adoptees' antisocial/hostile behaviors. Results also suggest that the adoptee's antisocial/hostile behavior and adoptive mother's parenting practices affect each other. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
78.
Thermionic power generation is a safe and clean energy source that allows for converting heat into electrical energy using thermionic electrons. The miniaturization is an advantage of this technology that led to the recent development of micro-gap thermionic power generators. In this work, thermal contact resistances between the micro-gap insulators and the emitter as well as between the micro-gap insulators and the collector are measured. A thermal resistance of 48.6 K/W is obtained by downsizing the insulators until 60 × 45 μm2 of contact area with the emitter, demonstrating a high impact for decreasing the micro-gap conduction heat loss density from the emitter to the collector from 28 W/cm2 (theoretical value obtained without considering contact resistances) to 5.6 W/cm2. Downsizing the contact area between the insulators and the emitter from 320 × 300 to 60 × 45 μm2 leads to an increase of the power conversion efficiency from 9.1 × 10?5 until 1.5 × 10?3. 相似文献
79.
Nowadays, due to rapid prototyping processes improvements, a functional metal part can be built directly by Additive Manufacturing. It is now accepted that these new processes can increase productivity while enabling a mass and cost reduction and an increase of the parts functionality. However, the physical phenomena that occur during these processes have a strong impact on the quality of the produced parts. Especially, because the manufacturing paths used to produce the parts lead these physical phenomena, it is essential to considerate them right from the parts design stage. In this context, a new numerical chain based on a new design for Additive Manufacturing (DFAM) methodology is proposed in this paper, the new DFAM methodology being detailed; both design requirements and manufacturing specificities are taken into account. The corresponding numerical tools are detailed in the particular case of thin-walled metal parts manufactured by an Additive Laser Manufacturing (ALM) process. 相似文献
80.
交织多址(IDMA)是一种依据交织器来区分多用户的多址接入技术.采用串行干扰抑制时,IDMA的收敛速度高,性能好,但其复杂度相对于并行干扰抑制要高.针对该问题,提出一种分组串行IDMA干扰抑制算法(GSIC-IDMA).该算法根据分组方法在系统性能和复杂度及时延间取得了较好的折中.此外,为了分析和研究GSIC-IDMA算法的性能及功率分配,本文推导出一种复杂度低的SNR演进算法.其较好地预测了GSIC-IDMA的性能. 相似文献