全文获取类型
收费全文 | 447篇 |
免费 | 47篇 |
国内免费 | 47篇 |
专业分类
化学 | 281篇 |
晶体学 | 4篇 |
力学 | 64篇 |
综合类 | 3篇 |
数学 | 43篇 |
物理学 | 146篇 |
出版年
2024年 | 2篇 |
2023年 | 11篇 |
2022年 | 12篇 |
2021年 | 10篇 |
2020年 | 17篇 |
2019年 | 16篇 |
2018年 | 12篇 |
2017年 | 8篇 |
2016年 | 23篇 |
2015年 | 24篇 |
2014年 | 28篇 |
2013年 | 38篇 |
2012年 | 43篇 |
2011年 | 37篇 |
2010年 | 19篇 |
2009年 | 25篇 |
2008年 | 28篇 |
2007年 | 32篇 |
2006年 | 29篇 |
2005年 | 27篇 |
2004年 | 14篇 |
2003年 | 8篇 |
2002年 | 16篇 |
2001年 | 6篇 |
2000年 | 4篇 |
1999年 | 13篇 |
1998年 | 4篇 |
1997年 | 6篇 |
1996年 | 8篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1979年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有541条查询结果,搜索用时 0 毫秒
1.
Wang X Zhang J Song A Lebrilla CB Lam KS 《Journal of the American Chemical Society》2004,126(18):5740-5749
In the "one-bead one-compound" (OBOC) combinatorial library method, each compound bead displays only one compound entity. Hundreds of thousands to millions of compound beads can be synthesized rapidly and screened simultaneously. Positive compound beads are then isolated for structural analysis. To fully exploit the power of OBOC combinatorial small molecule libraries, a robust and high throughput encoding method is needed to decode the positive compound beads. In this paper, we report on the development of a novel encoding strategy that combines the concepts of ladder-synthesis and chemical encoding on bilayer beads. In these encoded libraries, small molecule compounds are displayed on the bead surface, and cleavable coding tags consisting of a series of truncated molecules reside in the bead interior. Such a library can be easily constructed using the biphasic approach (J. Am. Chem. Soc.2002, 124, 7678) to topologically segregate the functionalities of the beads during library synthesis. The ladder members and coding tags are then released for MALDI-TOF-MS analysis. To simplify the interpretation of the mass spectra, we purposely add bromine into the cleavable linker so that the cleavage products generate a characteristic isotope fingerprint. The chemical structure of library compounds can be determined by analyzing the mass differences between adjacent peaks on the mass spectra. This encoding strategy also provides valuable information on the quality of the testing compound on the surface of the bead. To validate this methodology, a model OBOC small molecule library with 12,288 members was synthesized on TentaGel beads and screened against streptavidin. The chemical structures of the compound on each positive bead were unambiguously identified. 相似文献
2.
Tao Yu Xiaojie Jiang Xiaobo Xu Congyi Jiang Rui Kang Xiaobing Jiang 《Molecules (Basel, Switzerland)》2022,27(10)
Listeria monocytogenes is a major foodborne pathogen that can cause listeriosis in humans and animals. Andrographolide is known as a natural antibiotic and exhibits good antibacterial activity. We aimed to investigate the effect of andrographolide on two quorum-sensing (QS) systems, LuxS/AI-2 and Agr/AIP of L. monocytogenes, as well as QS-controlled phenotypes in this study. Our results showed that neither luxS expression nor AI-2 production was affected by andrographolide. Nevertheless, andrographolide significantly reduced the expression levels of the agr genes and the activity of the agr promoter P2. Results from the crystal violet staining method, confocal laser scanning microscopy (CLSM), and field emission scanning electron microscopy (FE-SEM) demonstrated that andrographolide remarkably inhibited the biofilm-forming ability of L. monocytogenes 10403S. The preformed biofilms were eradicated when exposed to andrographolide, and reduced surviving cells were also observed in treated biofilms. L. monocytogenes treated with andrographolide exhibited decreased ability to secrete LLO and adhere to and invade Caco-2 cells. Therefore, andrographolide is a potential QS inhibitor by targeting the Agr QS system to reduce biofilm formation and virulence of L. monocytogenes. 相似文献
3.
左手材料设计及透明现象研究进展 总被引:2,自引:0,他引:2
左手材料具有负的介电常数, 磁导率和折射率,它与电磁波相互作用的规律与传统材料有本质的区别.首先讨论了金属线点阵结构实现负介电常数和开口谐振环点阵结构实现负磁导率的内在机理,综述了目前实现左手材料的设计与制备方法,讨论了左手材料研究中能量如何定义以满足守恒律, 左手材料的宏观等效参数的确定,以及影响左手材料负折射相对频带带宽的因素。最后对左手材料在光子隧道效应和电磁波透明方面的应用进行了介绍,重点讨论了利用力学中的``中性夹杂'概念对电磁波透明的设计.论文还探讨了声波左手材料的概念和物理意义,介绍了用声波左手材料实现声波透明的方法. 相似文献
4.
5.
Yuan Haifeng Zhao Yan Yang Chan Zhang Cheng Yang Yue Meng Hongmin Huan Shuangyan Song Guosheng Zhang Xiaobing 《中国科学:化学(英文版)》2020,63(7):924-935
For chemotherapy, drug delivery systems often suffer from the inefficient drug loading capability, which usually cause systems toxicity and extra burden to excrete carrier itself. Moreover, the cancer therapeutic efficacy is also greatly limited by the specificity of tumor microenvironment for reactive oxygen species(ROS) based cancer therapeutic strategy(e.g., chemodynamic therapy). Herein, we have developed metal-drug coordination nanoplatform that can not only be responsive to tumor microenvironment but also modulate it, so as to achieve efficient treatment of cancer. Excitingly, by employing small molecule drug(6-thioguanine) as ligand copper ions, we achieve a high drug loading rate(60.1%) and 100% of utilization of metal-drug coordination nanoplatform(Cu-TG). Interestingly, Cu-TG possessed high-efficiently horseradish peroxidase-like, glutathione peroxidase-like and catalase-like activity. Under the tumor microenvironment, Cu-TG exhibited the self-reinforcing circular catalysis that is able to amplify the cellular oxidative stress, inducing notable cancer cellular apoptosis. Moreover, Cu-TG could be activated with glutathione(GSH) and facilitated for GSH triggered 6-TG release, higher selective therapeutic effect toward cancer cells, and GSH activated T_1 weight-magnetic resonance imaging. Based on the above properties, Cu-TG exhibited magnetic resonance imaging(MRI) guiding, efficient and synergistic combination of chemodynamic and chemotherapy with self-reinforcing therapeutic outcomes in vivo. 相似文献
6.
7.
本文通过56.4MHz19F的核磁共振波谱对全氟聚甲乙醚的结构进行了初步研究。根据谱图上所出现的21条共振吸收峰,基本上确定了各峰的归宿。并在仪器分辨率所能达到的情况下,分别归纳出全氟聚甲乙醚不同单元组的序列分布,同时对聚合物链的未端结构也进行了探讨。 相似文献
8.
Sonodynamic therapy (SDT) is a novel tumor therapy method. We investigated membrane fluidity, activity of the enzymes and membrane morphology in vitro post hematoporphyrin-SDT treatment. Furthermore, the potential mechanisms behind the changes in membrane fluidity and enzymic activity were discussed. Tumor cells were exposed to ultrasound at 1.75 MHz for up to 3 min in the presence and absence of hematoporphyrin. Fluorescence polarization, contents of Malonaldehyde, and levels of free fatty acid were assessed. Activity of enzymes was checked by the plumbic nitrate detection method. For the morphologic study, a scanning electron microscope was used to observe the cellular surface. Ultrasonically induced cell damage increased in the presence of HPD (from 15% to 24%). Compared with ultrasound treatment alone, the fluidity decreased from 5.037 to 3.908, malonaldehyde content and free fatty acid level increased from 0.743 nmol/mL to 0.979 nmol/mL and from 237.180 μmol/L to 730.769 μmol/L, respectively, post ultrasound combined with HPD treatment. Inactivity of adenylate cyclase and guanylate cyclase and significant deformation of the cellular surface were also observed post SDT treatment. Our results suggested that alterations in membrane modality and lipid composition played important roles in SDT-mediated inhibition of tumor growth, even inducing tumor cell death, which might be attributed to a sono-chemical activation mechanism. 相似文献
9.
Hanghang Wang Haiyan Li Yonggao Zheng Pengcheng Lian Prof. Dr. Xiaobing Wan 《Chemistry (Weinheim an der Bergstrasse, Germany)》2019,25(9):2195-2198
In this communication, an unprecedented interception of CnF2n+1(O)SO. radical with a copper-based carbene has been established. Distinguished by wide substrate scopes and mild reaction conditions, this novel radical–carbene coupling reaction (RCC reaction) provides a fundamentally different and mechanistically interesting strategy for the synthesis of perfluoroalkanesulfinate esters. 相似文献
10.
“知行统一” 的观念在教育界已深入人心,但是要做到切实履行却非易事。经过为期九年的精心打造,上海交通大学开设的创新型实践课程“结构模型设计与制作” 初步实现了“学与行” 的有机融合,教学效果显著,深受学生欢迎。本文是对该课程的总结与反思,希望对我国相关工科教学改革起到有益的借鉴作用。 相似文献