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161.
Discovery of Quinoline‐Derived Trifluoromethyl Alcohols,Determination of Their in vivo Toxicity and Anticancer Activity in a Zebrafish Embryo Model 下载免费PDF全文
Prof. Dr. Vinoth Sittaramane Jihan Padgett Philip Salter Ashley Williams Shauntelle Luke Rebecca McCall Prof. Dr. Jonathan F. Arambula Vincent B. Graves Mark Blocker David Van Leuven Keturah Bowe Julia Heimberger Hannah C. Cade Supriya Immaneni Prof. Dr. Abid Shaikh 《ChemMedChem》2015,10(11):1802-1807
In this study the rational design, synthesis, and anticancer activity of quinoline‐derived trifluoromethyl alcohols were evaluated. Members of this novel class of trifluoromethyl alcohols were identified as potent growth inhibitors in a zebrafish embryo model. Synthesis of these compounds was carried out with an sp3‐C?H functionalization strategy of methyl quinolines with trifluoromethyl ketones. A zebrafish embryo model was also used to explore the toxicity of ethyl 4,4,4‐trifluoro‐3‐hydroxy‐3‐(quinolin‐2‐ylmethyl)butanoate ( 1 ), 2‐benzyl‐1,1,1‐trifluoro‐3‐(quinolin‐2‐yl)propan‐2‐ol ( 2 ), and trifluoro‐3‐(isoquinolin‐1‐yl)‐2‐(thiophen‐2‐yl)propan‐2‐ol ( 3 ). Compounds 2 and 3 were found to be more toxic than compound 1 ; apoptotic staining assays indicated that compound 3 causes increased cell death. In vitro cell proliferation assays showed that compound 2 , with an LC50 value of 14.14 μm , has more potent anticancer activity than cisplatin. This novel class of inhibitors provides a new direction in the discovery of effective anticancer agents. 相似文献
162.
Cover Picture: Discovery of MK‐8970: An Acetal Carbonate Prodrug of Raltegravir with Enhanced Colonic Absorption (ChemMedChem 2/2015) 下载免费PDF全文
Dr. Abbas M. Walji Dr. Rosa I. Sanchez Dr. Sophie‐Dorothee Clas Dr. Rebecca Nofsinger Dr. Manuel de Lera Ruiz Dr. Jing Li Dr. Amrithraj Bennet Christopher John Dr. David Jonathan Bennett Dr. John M. Sanders Christina N. Di Marco Somang Hope Kim Dr. Jaume Balsells Scott S. Ceglia Dr. Qun Dang Kimberly Manser Becky Nissley Dr. John S. Wai Dr. Michael Hafey Junying Wang Gene Chessen Dr. Allen Templeton Dr. John Higgins Dr. Ronald Smith Dr. Yunhui Wu Dr. Jay Grobler Dr. Paul J. Coleman 《ChemMedChem》2015,10(2):213-213
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Zhongxiao Wan Dorrian Mah Svetlana Simtchouk Andreas Kluftinger Jonathan P. Little 《International journal of molecular sciences》2015,16(1):1221-1231
Adipose tissue secretes numerous hormone-like factors, which are known as adipokines. Adipokine receptors have been identified in the central nervous system but the potential role of adipokine signaling in neuroprotection is unclear. The aim of this study is to determine (1) Whether adipokines secreted from cultured adipose tissue of lean humans is protective against oxidative stress-induced neurotoxicity in human SH-SY5Y neuronal cells; and (2) To explore potential signaling pathways involved in these processes. Adipose tissue conditioned media (ATCM) from healthy lean subjects completely prevented H2O2 induced neurotoxicity, while this effect is lost after heating ATCM. ATCM activated the phosphorylation of ERK1/2, JNK and Akt at serine 308 in SH-SY5Y cells. PD98059 (25 µM), SP600125 (5 µM) and LY29400 (20 µM) partially blocked the protective effects of ATCM against H2O2 induced neurotoxicity. Findings demonstrate that heat-sensitive factors secreted from human adipose tissue of lean subjects are protective against H2O2 induced neurotoxicity and ERK1/2, JNK, and PI3K signaling pathways are involved in these processes. In conclusion, this study demonstrates preliminary but encouraging data to further support that adipose tissue secreted factors from lean human subjects might possess neuroprotective properties and unravel the specific roles of ERK1/2, JNK and PI3K in these processes. 相似文献
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Dr. Ying‐Ying Huang Dr. Thiagarajan Balasubramanian Dr. Eunkyung Yang Dr. Dianzhong Luo Dr. James R. Diers Prof. David F. Bocian Prof. Jonathan S. Lindsey Prof. Dewey Holten Dr. Michael R. Hamblin 《ChemMedChem》2012,7(12):2155-2167
A series of four stable synthetic bacteriochlorins was tested in vitro in HeLa cells for their potential in photodynamic therapy (PDT). The parent bacteriochlorin (BC), dicyano derivative (NC)2BC and corresponding zinc chelate (NC)2BC–Zn and palladium chelate (NC)2BC–Pd were studied. Direct dilution of a solution of bacteriochlorin in an organic solvent (N,N‐dimethylacetamide) into serum‐containing medium was compared with the dilution of bacteriochlorin in Cremophor EL (CrEL; polyoxyethylene glycerol triricinoleate) micelles into the same medium. CrEL generally reduced aggregation (as indicated by absorption and fluorescence) and increased activity up to tenfold (depending on bacteriochlorin), although it decreased cellular uptake. The order of PDT activity against HeLa human cancer cells after 24 h incubation and illumination with 10 J cm?2 of near‐infrared (NIR) light is (NC)2BC–Pd (LD50=25 nM ) > (NC)2BC > (NC)2BC–Zn ≈ BC. Subcellular localization was determined to be in the endoplasmic reticulum, mitochondria and lysosomes, depending on the bacteriochlorin. (NC)2BC–Pd showed PDT‐mediated damage to mitochondria and lysosomes, and the greatest production of hydroxyl radicals as determined using a hydroxyphenylfluorescein probe. The incorporation of cyano substituents provides an excellent motif for the enhancement of the photoactivity and photostability of bacteriochlorins as PDT photosensitizers. 相似文献
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Computer rendering and visual detection of orange peel 总被引:1,自引:0,他引:1
The computer graphic simulation of a common spray painting artifact, called orange peel, is discussed. Orange peel distorts surface reflections and is commonplace in product design applications. The orange peel measurements from a standard industrial instrument are used to construct a height field, and this surface is rendered using traditional normal mapping techniques. Comparisons are made between real panels with orange peel and simulations of those panels. A simple visual model for detecting the presence of orange peel is also presented and evaluated. User testing of the model confirms that orange peel is more visible on dark paint colors than on light paint colors. The latter outcome suggests that to minimize application time, but still keep orange peel below visual threshold, paint application systems should be designed to take paint color into account. 相似文献