全文获取类型
收费全文 | 3899篇 |
免费 | 222篇 |
国内免费 | 4篇 |
专业分类
电工技术 | 17篇 |
综合类 | 5篇 |
化学工业 | 801篇 |
金属工艺 | 22篇 |
机械仪表 | 36篇 |
建筑科学 | 163篇 |
矿业工程 | 7篇 |
能源动力 | 63篇 |
轻工业 | 469篇 |
水利工程 | 46篇 |
石油天然气 | 8篇 |
无线电 | 211篇 |
一般工业技术 | 647篇 |
冶金工业 | 1211篇 |
原子能技术 | 1篇 |
自动化技术 | 418篇 |
出版年
2024年 | 8篇 |
2023年 | 26篇 |
2022年 | 63篇 |
2021年 | 100篇 |
2020年 | 70篇 |
2019年 | 65篇 |
2018年 | 93篇 |
2017年 | 96篇 |
2016年 | 100篇 |
2015年 | 103篇 |
2014年 | 124篇 |
2013年 | 233篇 |
2012年 | 193篇 |
2011年 | 349篇 |
2010年 | 260篇 |
2009年 | 228篇 |
2008年 | 283篇 |
2007年 | 254篇 |
2006年 | 209篇 |
2005年 | 183篇 |
2004年 | 147篇 |
2003年 | 130篇 |
2002年 | 124篇 |
2001年 | 83篇 |
2000年 | 80篇 |
1999年 | 71篇 |
1998年 | 45篇 |
1997年 | 67篇 |
1996年 | 50篇 |
1995年 | 42篇 |
1994年 | 30篇 |
1993年 | 32篇 |
1992年 | 27篇 |
1991年 | 11篇 |
1990年 | 22篇 |
1989年 | 22篇 |
1988年 | 13篇 |
1987年 | 13篇 |
1986年 | 14篇 |
1985年 | 14篇 |
1984年 | 11篇 |
1983年 | 11篇 |
1982年 | 2篇 |
1981年 | 6篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1975年 | 5篇 |
1972年 | 1篇 |
排序方式: 共有4125条查询结果,搜索用时 0 毫秒
91.
Dichlorophenylacrylonitriles as AhR Ligands That Display Selective Breast Cancer Cytotoxicity in vitro 下载免费PDF全文
Jennifer R. Baker Dr. Jayne Gilbert Prof. Stefan Paula Dr. Xiao Zhu Dr. Jennette A. Sakoff Prof. Adam McCluskey 《ChemMedChem》2018,13(14):1447-1458
Knoevenagel condensation of 3,4‐dichloro‐ and 2,6‐dichlorophenylacetonitriles gave a library of dichlorophenylacrylonitriles. Our leads (Z)‐2‐(3,4‐dichlorophenyl)‐3‐(1H‐pyrrol‐2‐yl)acrylonitrile ( 5 ) and (Z)‐2‐(3,4‐dichlorophenyl)‐3‐(4‐nitrophenyl)acrylonitrile ( 6 ) displayed 0.56±0.03 and 0.127±0.04 μm growth inhibition (GI50) and 260‐fold selectivity for the MCF‐7 breast cancer cell line. A 2,6‐dichlorophenyl moiety saw a 10‐fold decrease in potency; additional nitrogen moieties (‐NO2) enhanced activity (Z)‐2‐(2,6‐dichloro‐3‐nitrophenyl)‐3‐(2‐nitrophenyl)acrylonitrile ( 26 ) and (Z)‐2‐(2,6‐dichloro‐3‐nitrophenyl)‐3‐(3‐nitrophenyl)acrylonitrile ( 27 ), with the corresponding ‐NH2 analogues (Z)‐2‐(3‐amino‐2,6‐dichlorophenyl)‐3‐(2‐aminophenyl)acrylonitrile ( 29 ) and (Z)‐2‐(3‐amino‐2,6‐dichlorophenyl)‐3‐(3‐aminophenyl)acrylonitrile ( 30 ) being more potent. Despite this, both 29 (2.8±0.03 μm ) and 30 (2.8±0.03 μm ) were found to be 10‐fold less cytotoxic than 6 . A bromine moiety effected a 3‐fold enhancement in solubility with (Z)‐3‐(5‐bromo‐1H‐pyrrol‐2‐yl)‐2‐(3,4‐dichlorophenyl)acrylonitrile 18 relative to 5 at 211 μg mL?1. Modeling‐guided synthesis saw the introduction of 4‐aminophenyl substituents (Z)‐3‐(4‐aminophenyl)‐2‐(3,4‐dichlorophenyl)acrylonitrile ( 35 ) and (Z)‐N‐(4‐(2‐cyano‐2‐(3,4‐dichlorophenyl)vinyl)phenyl)acetamide ( 38 ), with respective GI50 values of 0.030±0.014 and 0.034±0.01 μm . Other analogues such as 35 and 36 were found to have sub‐micromolar potency against our panel of cancer cell lines (HT29, colon; U87 and SJ‐G2, glioblastoma; A2780, ovarian; H460, lung; A431, skin; Du145, prostate; BE2‐C, neuroblastoma; MIA, pancreas; and SMA, murine glioblastoma), except compound 38 against the U87 cell line. A more extensive evaluation of 38 ((Z)‐N‐(4‐(2‐cyano‐2‐(3,4‐dichlorophenyl)vinyl)phenyl)acetamide) in a panel of drug‐resistant breast carcinoma cell lines showed 10–206 nm potency against MDAMB468, T47D, ZR‐75‐1, SKBR3, and BT474. Molecular Operating Environment docking scores showed a good correlation between predicted binding efficiencies and observed MCF‐7 cytotoxicity. This supports the use of this model in the development of breast‐cancer‐specific drugs. 相似文献
92.
Surrogate endpoints in oncology research and practice have garnered increasing attention over the past two decades. This activity has largely been driven by the promise surrogate endpoints appear to hold: the potential to get new therapies to seriously ill patients more rapidly. However, uncertainties abound. Even agreeing upon a definition of a "valid" surrogate endpoint has not been a straightforward exercise; this article begins by highlighting differences in how this term has been previously captured and applied, as well as laying out the basic criteria essential for its application in advanced colorectal cancer. Ideally, these elements include (but are not limited to) ease of measurement, rapid indication of treatment effect, and, most importantly, reliable and consistent prediction of the true impact of a treatment on the ultimate outcome of interest: overall survival. The strengths and weaknesses of current potential surrogate endpoints in advanced colorectal cancer, including performance status, carcinoembryonic antigen plasma level, overall response rate, time to progression, and disease-free survival, are each considered in turn. Finally, limitations of surrogate endpoints in the clinical setting, including challenges in extrapolation to new therapies, and the incomplete provision of information about potential adverse effects, are discussed. Work remains to be done between physicians and statisticians to bridge the gap between that which is statistically demonstrable and that which will be clinically useful.The term ;surrogate endpoint' was virtually unknown by most oncologists 15 years ago. A search in PubMed [http://www.ncbi.nlm.nih.gov] based on the words ;surrogate and cancer' shows that more than 2000 papers were published in medical journals in the last 20 years, with a dramatic increase of interest in the last five years. Interestingly, the same trend is observed when the words ;surrogate and heart' are entered into PubMed, suggesting that the issue of surrogate endpoints goes beyond the field of oncology, although the frequency of discussion varies (Figure 1; note different y-axis scales for oncology and cardiology).The goal of the present paper is to discuss the main issues surrounding surrogate endpoints from a clinician's point of view, using as an example surrogate endpoints of overall survival (OS) in advanced colorectal cancer (ACC). 相似文献
93.
Hendrikus A. Visser Ton C. Bor Mannes Wolters Tom A. P. Engels Leon E. Govaert 《大分子材料与工程》2010,295(7):637-651
The most widespread application of polymers in structural applications is their use as pipe material for e.g., gas distribution systems. Pipes have a design lifetime of typically 50 years, which rules out real‐time lifetime assessment methods. Here, an engineering approach is presented, which makes it possible to predict long‐term ductile failure of loaded glassy polymers based on short‐term tests. The approach is based upon the hypothesis that failure is governed by accumulation of plastic deformation up to a critical strain. A pressure‐modified Eyring relation is employed to calculate the accumulation of plastic strain for any simple loading geometry. It is demonstrated that the approach can produce accurate quantitative time‐to‐failure predictions for loaded PC specimens and uPVC pipe segments.
94.
Christine Feillet-Coudray Gilles Fouret Claire Vigor Béatrice Bonafos Bernard Jover Agnieszka Blachnio-Zabielska Jennifer Rieusset François Casas Sylvie Gaillet Jean Francois Landrier Thierry Durand Charles Coudray 《Lipids》2019,54(1):81-97
Inflammation and oxidative stress are thought to be involved in, or associated with, the development of obesity, dyslipidemia, hepatic steatosis, and insulin resistance. This work was designed to determine the evolution of inflammation and oxidative stress during onset and progression of hepatic steatosis and glucose intolerance. Seventy-five male Wistar rats were divided to control and high-fat high-fructose (HFHFr) groups. A subgroup of each group was sacrificed at 4, 8, 12, 16, and 20 weeks. HFHFr-fed rats exhibited overweight, glucose intolerance, and hepatic steatosis with increased contents of hepatic diacylglycerols and ceramides. The HFHFr diet increased hepatic interleukin 6 (IL-6) protein and adipose tissue CCL5 gene expression and hepatic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity but not mitochondrial reactive oxygen species (ROS) production. The HFHFr diet decreased plasma and liver levels of isoprostanoid metabolites as well as plasma thiobarbituric acid-reactive substance (TBARS) levels. Hepatic glutathione content was decreased with a moderate decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) with the HFHFr diet. Overall, HFHFr diet led to hepatic lipid accumulation and glucose intolerance, which were accompanied by only moderate inflammation and oxidative stress. Most of these changes occurred at the same time and as early as 8 or 12 weeks of diet treatment. This implies that oxidative stress may be the result, not the cause, of these metabolic alterations, and suggests that marked hepatic oxidative stress should probably occur at the end of the steatotic stage to result in frank insulin resistance and steatohepatitis. These findings need to be further evaluated in other animal species as well as in human studies. 相似文献
95.
Reiner JL O'Connell SG Moors AJ Kucklick JR Becker PR Keller JM 《Environmental science & technology》2011,45(19):8129-8136
Wildlife from remote locations have been shown to bioaccumulate perfluorinated compounds (PFCs) in their tissues. Twelve PFCs, consisting of perfluorinated carboxylic (PFCA) and sulfonic (PFSA) acids as well as the perfluorooctane sulfonate (PFOS) precursor perfluorooctane sulfonamide (PFOSA), were measured in livers of 68 beluga whales (Delphinapterus leucas) collected from two subpopulations, Cook Inlet and eastern Chukchi Sea, in Alaska between 1989 and 2006. PFOS and PFOSA were the dominant compounds measured in both beluga stock populations, with overall median concentrations of 10.8 ng/g and 22.8 ng/g, respectively. Long-chain perfluorocarboxylates, PFCAs (9 to 14 carbons), were detected in more than 80% of the samples. Perfluoroundecanoic acid (PFUnA) and perfluorotridecanoic acid (PFTriA) made up a large percentage of the PFCAs measured with median concentrations of 8.49 ng/g and 4.38 ng/g, respectively. To compare differences in location, year, sex, and length, backward stepwise multiple regression models of the individual and total PFC concentrations were used. Spatially, the Cook Inlet belugas had higher concentrations of most PFCAs and PFOS (p < 0.05); however, these belugas had a lower median concentration of PFOSA when compared to belugas from the eastern Chukchi Sea (p < 0.05). Temporal trends indicated most PFCAs, PFHxS, PFOS, and PFOSA concentrations increased from 1989 to 2006 (p < 0.05). Males had significantly higher concentrations of PFTriA, ΣPFCA, and PFOS (p < 0.05). Perfluorononanic acid (PFNA) and PFOS showed a significant decrease in concentration with increasing animal length (p < 0.05). These observations suggest the accumulation of PFCs in belugas is influenced by year, location, sex, and length. 相似文献
96.
Mice Fed a High‐Cholesterol Diet Supplemented with Quercetin‐3‐Glucoside Show Attenuated Hyperlipidemia and Hyperinsulinemia Associated with Differential Regulation of PCSK9 and LDLR in their Liver and Pancreas 下载免费PDF全文
97.
Solvatochromic merocyanine dyes were immobilized onto polymer surfaces and copolymerized with acrylic resins, yielding novel reversibly solvatochromic polymers, which were used as solvent polarity indicators that exhibited different colors in water and alcohols. To generate solvatochromic polymer for solvent polarity indication, two solvatochromic merocyanine dyes containing moieties, which allow their immobilization onto polymer surfaces, or copolymerization with acrylic and vinyl monomers, were sequentially synthesized in four and six steps. Merocyanine dye (E)‐2‐(2‐(1‐(6‐aminohexyl)pyridinium‐4‐yl)vinyl)‐4,6‐dichlorophenolate (AHPVD) was prepared with a terminal aminohexyl group which allowed covalent bonding to activated carboxylated or sulfonated polymeric materials. The dyes were covalently bonded to the polymer surfaces, such as, nylon, polycarbonate, polyethylene terephthalate, and silicone. Solvatochromic merocyanine dye (E)‐2‐(2‐(1‐(6‐acrylamidohexyl)pyridinium‐4‐yl)vinyl)‐4,6‐dichlorophenolate (AAPVD) was synthesized for radical copolymerization with acrylate and vinyl monomers and oligomers. Side‐chain solvatochromic merocyanine‐containing hydrophilic polymers with differential water and alcohol absorption were obtained upon photoinitiated radical copolymerization with specially formulated acrylated resins. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44451. 相似文献
98.
Dai J Park G Perry JL Il'ichev YV Bow DA Pritchard JB Faucet V Pfohl-Leszkowicz A Manderville RA Simon JD 《Accounts of chemical research》2004,37(11):874-881
Ochratoxins are a class of naturally occurring compounds produced by several fungi. The most toxic is ochratoxin A (OTA), and occurrence of some human nephropathies and tumors correlate with enhanced OTA exposure. In this Account, the following areas are examined: molecular details of the binding of OTA to human serum albumin (HSA), the influences of binding to HSA on the trans-port of OTA across epithelial cell membranes by organic anion transport proteins, the oxidative activation of OTA, and the formation of OTA adducts with biological molecules. These studies are beginning to provide a detailed chemical model for the trans-port, accumulation, and genotoxic and carcinogenic effects of OTA. 相似文献
99.
In 2012 Arian Foster, a running back for the Houston Texans of the National Football League (NFL), announced via Twitter that he is “officially a vegan now” (Foster, July 6, 2012). Foster's announcement precipitated a torrent of attention by many who worriedly debated the impact that his new diet may have on his on-field performance. In this article, we unravel the threads that have woven together a picture of who Foster is and what his decision to go vegan means. We argue that a close look at the media response reveals deeply held beliefs about masculinity, race, class, and place and the ways in which food serves in the constitution of subjectivity in the context of pro-football in Texas. We conduct a contextual discourse analysis of the popular and sports media coverage of Foster's diet using an intersectional framework to elaborate how normative masculinity is further nuanced by the meanings attributed to race, place, sexuality, sport, aggression, violence, health, and productivity. 相似文献
100.
D. Grant Willhite Jennifer R. Brigati Katie E. Selcer Joshua E. Denny Zachary A. Duck Stephen E. Wright 《Yeast (Chichester, England)》2014,31(9):361-374
Many fungi have evolved mechanisms to assess environmental nutrient availability prior to the energy‐intensive process of mating. In this study, we examined one such system in Saccharomyces cerevisiae, involving a glucose‐sensing pathway mediated by Gpr1p and the pheromone‐induced mating pathway. Initially we observed that the mating pathway in MATa cells is sensitive to environmental glucose depletion. This phenomenon can be partially reversed with a high glucose spike, but not with the addition of low levels of glucose. Deletion of the low‐affinity glucose receptor, Gpr1p, eliminated this glucose‐induced recovery of pheromone responsiveness. We then determined the impact of GPR1 deletion on the mating pathway and observed that, in all end points studied, the mating pathway response to pheromone is reduced in the absence of Gpr1p. Similarly, elimination of the Gα for Gpr1p, Gpa2p, resulted in reduction in pheromone sensitivity in all assays studied. The negative effect of removing Gpr1p on mating pathway activation could be recovered by overexpressing the mating receptor, Ste2p. Furthermore, Ste2p levels are reduced in the absence of glucose and GPR1. These data suggest that activity of the GPCR‐mediated mating pathway in S. cerevisiae is modulated by extracellular glucose concentrations through the only other GPCR in MATa cells, Gpr1p. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献