全文获取类型
收费全文 | 536篇 |
免费 | 4篇 |
国内免费 | 3篇 |
专业分类
化学 | 328篇 |
晶体学 | 3篇 |
力学 | 99篇 |
数学 | 21篇 |
物理学 | 92篇 |
出版年
2022年 | 2篇 |
2021年 | 1篇 |
2020年 | 9篇 |
2019年 | 2篇 |
2018年 | 3篇 |
2017年 | 2篇 |
2016年 | 5篇 |
2015年 | 1篇 |
2014年 | 12篇 |
2013年 | 11篇 |
2012年 | 29篇 |
2011年 | 32篇 |
2010年 | 16篇 |
2009年 | 12篇 |
2008年 | 32篇 |
2007年 | 16篇 |
2006年 | 24篇 |
2005年 | 37篇 |
2004年 | 24篇 |
2003年 | 52篇 |
2002年 | 27篇 |
2001年 | 14篇 |
2000年 | 17篇 |
1999年 | 15篇 |
1998年 | 7篇 |
1997年 | 10篇 |
1996年 | 7篇 |
1995年 | 8篇 |
1994年 | 4篇 |
1993年 | 8篇 |
1992年 | 15篇 |
1991年 | 14篇 |
1990年 | 8篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 8篇 |
1983年 | 6篇 |
1982年 | 8篇 |
1981年 | 9篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1973年 | 4篇 |
1937年 | 1篇 |
排序方式: 共有543条查询结果,搜索用时 15 毫秒
71.
Culture of cells as three-dimensional (3D) aggregates can enhance in vitro tests for basic biological research as well as for therapeutics development. Such 3D culture models, however, are often more complicated, cumbersome, and expensive than two-dimensional (2D) cultures. This paper describes a 384-well format hanging drop culture plate that makes spheroid formation, culture, and subsequent drug testing on the obtained 3D cellular constructs as straightforward to perform and adapt to existing high-throughput screening (HTS) instruments as conventional 2D cultures. Using this platform, we show that drugs with different modes of action produce distinct responses in the physiological 3D cell spheroids compared to conventional 2D cell monolayers. Specifically, the anticancer drug 5-fluorouracil (5-FU) has higher anti-proliferative effects on 2D cultures whereas the hypoxia activated drug commonly referred to as tirapazamine (TPZ) are more effective against 3D cultures. The multiplexed 3D hanging drop culture and testing plate provides an efficient way to obtain biological insights that are often lost in 2D platforms. 相似文献
72.
Douville NJ Zamankhan P Tung YC Li R Vaughan BL Tai CF White J Christensen PJ Grotberg JB Takayama S 《Lab on a chip》2011,11(4):609-619
Studies using this micro-system demonstrated significant morphological differences between alveolar epithelial cells (transformed human alveolar epithelial cell line, A549 and primary murine alveolar epithelial cells, AECs) exposed to combination of solid mechanical and surface-tension stresses (cyclic propagation of air-liquid interface and wall stretch) compared to cell populations exposed solely to cyclic stretch. We have also measured significant differences in both cell death and cell detachment rates in cell monolayers experiencing combination of stresses. This research describes new tools for studying the combined effects of fluid mechanical and solid mechanical stress on alveolar cells. It also highlights the role that surface tension forces may play in the development of clinical pathology, especially under conditions of surfactant dysfunction. The results support the need for further research and improved understanding on techniques to reduce and eliminate fluid stresses in clinical settings. 相似文献
73.
Yousuke Yamada Dr. Mariko Kitajima Dr. Noriyuki Kogure Dr. Sumphan Wongseripipatana Prof. Dr. Hiromitsu Takayama 《化学:亚洲杂志》2011,6(1):166-173
Seven new indole alkaloids were isolated from the roots of Gelsemium elegans Benth. and their structures were determined by spectroscopic analysis and chemical transformation from known alkaloids. Kounaminal ( 1 ) is a new koumine‐type alkaloid that contains an unusual aminal moiety. Humantenoxenine ( 2 ) and 15‐hydroxyhumantenoxenine ( 3 ) are humantenine‐type alkaloids that contain a novel β‐amino‐α,β‐unsaturated ketone residue. The other four novel alkaloids are two gelsedilam‐related and two gelsenicine‐related alkaloids. 相似文献
74.
Sakaki S Takayama T Sumimoto M Sugimoto M 《Journal of the American Chemical Society》2004,126(10):3332-3348
The Cp(2)Zr-catalyzed hydrosilylation of ethylene was theoretically investigated with DFT and MP2-MP4(SDQ) methods, to clarify the reaction mechanism and the characteristic features of this reaction. Although ethylene insertion into the Zr-SiH(3) bond of Cp(2)Zr(H)(SiH(3)) needs a very large activation barrier of 41.0 (42.3) kcal/mol, ethylene is easily inserted into the Zr-H bond with a very small activation barrier of 2.1 (2.8) kcal/mol, where the activation barrier and the energy of reaction calculated with the DFT(B3LYP) method are given and in parentheses are those values which have been corrected for the zero-point energy, hereafter. Not only this ethylene insertion reaction but also the coupling reaction between Cp(2)Zr(C(2)H(4)) and SiH(4) easily takes place to afford Cp(2)Zr(H)(CH(2)CH(2)SiH(3)) and Cp(2)Zr(CH(2)CH(3))(SiH(3)) with activation barriers of 0.3 (0.7) and 5.0 (5.4) kcal/mol, respectively. This coupling reaction involves a new type of Si-H sigma-bond activation which is similar to metathesis. The important interaction in the coupling reaction is the bonding overlap between the d(pi)-pi bonding orbital of Cp(2)Zr(C(2)H(4)) and the Si-H sigma orbital. The final step is neither direct C-H nor Si-C reductive elimination, because both reductive eliminations occur with a very large activation barrier and significantly large endothermicity. This is because the d orbital of Cp(2)Zr is at a high energy. On the other hand, ethylene-assisted C-H reductive elimination easily occurs with a small activation barrier, 5.0 (7.5) kcal/mol, and considerably large exothermicity, -10.6 (-7.1) kcal/mol. Also, ethylene-assisted Si-C reductive elimination and metatheses of Cp(2)Zr(H)(CH(2)CH(2)SiH(3)) and Cp(2)Zr(CH(2)CH(3))(SiH(3)) with SiH(4) take place with moderate activation barriers, 26.5 (30.7), 18.4 (20.5), and 28.3 (31.5) kcal/mol, respectively. From these results, it is clearly concluded that the most favorable catalytic cycle of the Cp(2)Zr-catalyzed hydrosilylation of ethylene consists of the coupling reaction of Cp(2)Zr(C(2)H(4)) with SiH(4) followed by the ethylene-assisted C-H reductive elimination. 相似文献
75.
An Efficient Method for the Conjugation of Hydrophilic and Hydrophobic Components by Solid‐Phase‐Assisted Disulfide Ligation 下载免费PDF全文
Kyohei Muguruma Takuya Shirasaka Daichi Akiyama Dr. Kentarou Fukumoto Dr. Akihiro Taguchi Dr. Kentaro Takayama Dr. Atsuhiko Taniguchi Prof. Yoshio Hayashi 《Angewandte Chemie (International ed. in English)》2018,57(8):2170-2173
Chemical conjugation between hydrophilic and hydrophobic components is difficult because of their extremely different solubility. Herein, we report a new versatile method with a solid‐phase‐assisted disulfide ligation to overcome the difficulty of conjugation attributed to solubility. The method involves two steps in a one‐pot process: 1) loading of a hydrophobic molecule onto a resin in an organic solvent, and 2) release of the solid‐supported hydrophobic molecule as a conjugate with a hydrophilic molecule into an aqueous solvent. This strategy allows the use of a suitable solvent system for the substrates in each step. Conjugates of a water‐insoluble drug, plinabulin, with hydrophilic carriers that could not be prepared by solution‐phase reactions were obtained in moderate yields (29–45 %). This strategy is widely applicable to the conjugation of compounds with solubility problems. 相似文献
76.
Takayama K Iwata M Hisamichi H Okamoto Y Aoki M Niwa A 《Chemical & pharmaceutical bulletin》2002,50(8):1050-1059
In order to develop novel and orally active phosphodiesterase (PDE) 4 inhibitors, random screening was performed using our chemical library to find YM-10335 possessing the 1,8-naphthyridin-2(1H)-one skeleton which is a completely different structure from rolipram. In this report, the syntheses and structure-activity relationships of the YM-10335 derivatives were described. Some compounds showed selective inhibitory activities for PDE 4 derived from human peripheral blood cells and no effect on the other PDE types (1, 2, 3, 5). The inhibition of the tumor necrosis factor-alpha (TNF-alpha) release in vitro and the carrageenan-induced pleurisy in rats were also described. 相似文献
77.
Takayama K Arakida Y Dixit T Iwashita T Kono T Nakamura E Otsuka K Shimosaki Y Torikai K Wake M 《Physical review letters》2007,98(5):054801
We report an experimental demonstration of the induction synchrotron, the concept of which has been proposed as a future accelerator for the second generation of neutrino factory or hadron collider. The induction synchrotron supports a superbunch and a superbunch permits more charge to be accelerated while observing the constraints of the transverse space-charge limit. By using a newly developed induction acceleration system instead of radio-wave acceleration devices, a single proton bunch injected from the 500 MeV booster ring and captured by the barrier bucket created by the induction step voltages was accelerated to 6 GeV in the KEK proton synchrotron. 相似文献
78.
Eguchi K Enomoto S Furuno K Goldman J Hanada H Ikeda H Ikeda K Inoue K Ishihara K Itoh W Iwamoto T Kawaguchi T Kawashima T Kinoshita H Kishimoto Y Koga M Koseki Y Maeda T Mitsui T Motoki M Nakajima K Nakajima M Nakajima T Ogawa H Owada K Sakabe T Shimizu I Shirai J Suekane F Suzuki A Tada K Tajima O Takayama T Tamae K Watanabe H Busenitz J Djurcic Z McKinny K Mei DM Piepke A Yakushev E Berger BE Chan YD Decowski MP Dwyer DA Freedman SJ Fu Y Fujikawa BK Heeger KM Lesko KT Luk KB Murayama H 《Physical review letters》2003,90(2):021802
KamLAND has measured the flux of nu;(e)'s from distant nuclear reactors. We find fewer nu;(e) events than expected from standard assumptions about nu;(e) propagation at the 99.95% C.L. In a 162 ton.yr exposure the ratio of the observed inverse beta-decay events to the expected number without nu;(e) disappearance is 0.611+/-0.085(stat)+/-0.041(syst) for nu;(e) energies >3.4 MeV. In the context of two-flavor neutrino oscillations with CPT invariance, all solutions to the solar neutrino problem except for the "large mixing angle" region are excluded. 相似文献
79.
Chiba J Iimura S Yoneda Y Sugimoto Y Horiuchi T Muro F Ochiai Y Ogasawara T Tsubokawa M Iigou Y Takayama G Taira T Takata Y Yokoyama M Takashi T Nakayama A Machinaga N 《Chemical & pharmaceutical bulletin》2006,54(11):1515-1529
A novel series of benzoic acid derivatives as VLA-4 antagonists were synthesized. Optimization, focusing on activity and lipophilicity needed for cell permeability, resulted in the identification of 15b and 15e with good activity (IC50 = 1.6 nM each) and moderate lipophilicity (Log D = 2.0, 1.8). Furthermore, 15e demonstrated efficacy in murine asthma model by an oral dose of 30 mg/kg. 相似文献
80.
Tsutomu Takeichi Hiroshi Yada Yuzi Takayama Masami Morikawa 《Journal of separation science》1995,18(10):630-634
A chiral stationary phase prepared by bonding L -valine-t-butylamide to XE-60 has been coated on glass and metal capillaries. The performances of the chiral glass and metal columns were equivalent to those of commercial fused silica capillary columns. The thermal stability of the glass column was examined up to 280°C. It was found that no appreciable change in separation factor (α value) was observed up to 230°C. The α values gradually decreased between 240 and 260°C, and enantiomer separation was no longer achieved at 280°C. It was concluded that the allowable upper limit temperature of the chiral stationary phase is between 230 and 240°C in the isothermal mode, and ca 260°C in temperature-programmed mode. 相似文献