全文获取类型
收费全文 | 671篇 |
免费 | 115篇 |
国内免费 | 17篇 |
专业分类
化学 | 781篇 |
综合类 | 1篇 |
数学 | 1篇 |
物理学 | 20篇 |
出版年
2024年 | 1篇 |
2023年 | 5篇 |
2022年 | 12篇 |
2021年 | 48篇 |
2020年 | 38篇 |
2019年 | 15篇 |
2018年 | 21篇 |
2017年 | 12篇 |
2016年 | 37篇 |
2015年 | 39篇 |
2014年 | 46篇 |
2013年 | 59篇 |
2012年 | 52篇 |
2011年 | 35篇 |
2010年 | 31篇 |
2009年 | 42篇 |
2008年 | 41篇 |
2007年 | 40篇 |
2006年 | 46篇 |
2005年 | 41篇 |
2004年 | 34篇 |
2003年 | 43篇 |
2002年 | 9篇 |
2001年 | 19篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
排序方式: 共有803条查询结果,搜索用时 15 毫秒
81.
82.
83.
84.
85.
There has been an increasing interest in the use of gallium in anticancer activity. However, whether the uptakes of two species of transferrin, including digallium transferrin (Ga2‐Tf) and the C‐terminal monogallium transferrin (GaC‐Tf) by cells, are different is not well understood. In this work the mechanism of both species passing in and out K562 cells has been established by using 125I‐labeled transferrin. There were about (1.5±0.08)×105 binding sites per cell surface. Both Ga2‐Tf and GaC‐Tf were recycled to the cell exterior with a protracted endocytic cycle compared to apotransferrin (apoTf). The cycling time from the internalization to release was calculated about t1/2= (3.15±0.055) min for apoTf, t1/2= (4.69±0.09) min for Ga2‐Tf and t1/2= (4.78±0.15) min for GaC‐Tf. The result implies that metal dissociating from transferrin in acidic endosomes was likely to be the key step. Both Ga2‐Tf and GaC‐Tf into K562 cells are transferrin receptor‐mediated process with a similar rate of endocytosis and release. Our present observations provide useful information for better targeted drugs in specific therapy. 相似文献
86.
87.
Dr. Xin Fang Ying Tong Di Yu Zhang Dr. Zhi Ping Xu Prof. Yang Lu Qian Qian Chen Prof. Qi Tai Zheng Prof. Dr. Xiao Jiang Hao 《Angewandte Chemie (International ed. in English)》2015,54(19):5592-5595
Perforalactone A ( 1 ), a new 20S quassinoid with a unique cagelike 2,4‐dioxaadamantane ring system and a migrated side chain, was isolated from the plant Harrisonia perforata together with two biosynthetically related new quassinoids. The structures of these natural products were elucidated by NMR spectroscopy, X‐ray diffraction analysis, computational modeling, and the CD excitation chirality method. The compounds exhibited notable biological properties, including insecticidal activity against Aphis medicaginis Koch and antagonist activity at the nicotinic acetylcholine receptor of Drosophila melanogaster. The structural features of these compounds may be related to their promising biological characteristics. Their biosynthesis and an alternative origin of quassinoid‐type natural products are also discussed. 相似文献
88.
Membrane receptors control fundamental cellular processes. Binding of a specific ligand to a receptor initiates communication through the membrane and activation of signaling cascades. This activation process often leads to a spatial rearrangement of receptors in the membrane at the molecular level. Single‐molecule techniques contributed significantly to the understanding of receptor organization and rearrangement in membranes. Here, we review four prominent single‐molecule techniques that have been applied to membrane receptors, namely, stepwise photobleaching, Förster resonance energy transfer, sub‐diffraction localization microscopy and co‐tracking. We discuss the requirements, benefits and limitations of each technique, discuss target labeling, present a selection of applications and results and compare the different methodologies. 相似文献
89.
Dr. Yong Zhang Dr. Huafei Zou Dr. Ying Wang Dawna Caballero Jose Gonzalez Elizabeth Chao Gus Welzel Dr. Weijun Shen Dr. Danling Wang Dr. Peter G. Schultz Dr. Feng Wang 《Angewandte Chemie (International ed. in English)》2015,54(7):2126-2130
Bovine antibody BLV1H12 possesses a unique “stalk–knob” architecture in its ultralong heavy chain CDR3, allowing substitutions of the “knob” domain with protein agonists to generate functional antibody chimeras. We have generated a humanized glucagon‐like peptide‐1 (GLP‐1) receptor agonist antibody by first introducing a coiled‐coil “stalk” into CDR3H of the antibody herceptin. Exendin‐4 (Ex‐4), a GLP‐1 receptor agonist, was then fused to the engineered stalk with flexible linkers, and a Factor Xa cleavage site was inserted immediately in front of Ex‐4 to allow release of the N‐terminus of the fused peptide. The resulting clipped herceptin–Ex‐4 fusion protein is more potent in vitro in activating GLP‐1 receptors than the Ex‐4 peptide. The clipped herceptin–Ex‐4 has an extended plasma half‐life of approximately four days and sustained control of blood glucose levels for more than a week in mice. This work provides a novel approach to the development of human or humanized agonist antibodies as therapeutics. 相似文献
90.
在B3LYP/6-311G基组水平下,运用密度泛函理论(DFT)的量子化学方法,对20种重氮乙烷新烟碱类杀虫剂分子的电子结构特征进行了研究,获得了它们的前线轨道能(EHOMO、ENHOMO、ELUMO、ENLUMO等)、原子电荷(Qi)、摩尔熵(Sm)、偶极矩(μ)等量化参数与物理性质。经最佳变量子集回归研究发现,重氮乙烷新烟碱类杀虫剂分子对果蝇n AChRs、哺乳动物α4β2亚型的亲和力常数(p KD、p KA)分别与ELUMO、QW、QF、QN等参数具有良好的线性关系。逐一或逐四剔除交互验证以及VIF、tα/2检验,所建2个QSAR模型具有良好的稳健性及预测能力。根据2个QSAR模型推断了重氮乙烷新烟碱类分子可能的杀虫机理。进一步研究发现,在重氮乙烷新烟碱类分子的吡啶环上的合适部位,选用不含复键的吸电子能力较强的取代基团对其进行结构修饰,有利于提高修饰后分子的生物活性。基于分子17,设计出4种经结构修饰后对果蝇n AChRs亲和力显著提高的重氮乙烷新烟碱类分子(分别是分子27,28,30和31),希望能得到实验的证实。 相似文献