全文获取类型
收费全文 | 1214篇 |
免费 | 85篇 |
出版年
2023年 | 6篇 |
2022年 | 11篇 |
2021年 | 35篇 |
2020年 | 19篇 |
2019年 | 22篇 |
2018年 | 31篇 |
2017年 | 29篇 |
2016年 | 33篇 |
2015年 | 62篇 |
2014年 | 62篇 |
2013年 | 82篇 |
2012年 | 92篇 |
2011年 | 91篇 |
2010年 | 61篇 |
2009年 | 53篇 |
2008年 | 56篇 |
2007年 | 62篇 |
2006年 | 65篇 |
2005年 | 46篇 |
2004年 | 55篇 |
2003年 | 31篇 |
2002年 | 38篇 |
2001年 | 32篇 |
2000年 | 24篇 |
1999年 | 24篇 |
1998年 | 13篇 |
1997年 | 7篇 |
1996年 | 9篇 |
1995年 | 6篇 |
1993年 | 7篇 |
1992年 | 8篇 |
1991年 | 5篇 |
1990年 | 9篇 |
1989年 | 8篇 |
1988年 | 8篇 |
1987年 | 9篇 |
1986年 | 7篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1982年 | 4篇 |
1980年 | 11篇 |
1979年 | 9篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1973年 | 3篇 |
1972年 | 5篇 |
1970年 | 5篇 |
1969年 | 4篇 |
1968年 | 4篇 |
排序方式: 共有1299条查询结果,搜索用时 15 毫秒
91.
92.
Dharmu I Ramamurty N Kannan R Babu M 《In vitro cellular & developmental biology. Animal》2007,43(8-9):306-314
The hemolymph-derived achatininH (lectin) from Achatina fulica showed a marked cytotoxic effect on MCF7, a human mammary carcinoma cell line. IC50 values as measured by the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay for achatininH ranged from 6 to 10 μg/ml in the MCF7 cells. MCF7 cells showed significant morphological changes leading to cell death. The
above cell death was observed after 48 h of treatment with 8 μg/ml when compared to untreated cells. Alterations in the tumor
marker enzymes, as well as in antioxidant enzymes, were observed after achatininH treatment. The specificity and purity of the achatininH was confirmed by the Western blot assay. AchatininH binding to MCF7 cells was detected by anti-achatininH, and visualization of the achatininH binding sites on confluent MCF7 cells was confirmed by flourescein isothiocyanate conjugated secondary antibody. MCF7-treated
cells fluoresced, indicating the presence of achatininH binding sites. Fluorescence-activated cell sorting analysis of the cell cycle showed a significant increase in S-phase in
MCF7 cells after 48 h of achatininH treatment. The cells were arrested in G2/M phase of the cell cycle after 48 h with significant changes in cell viability. Cellular damage was confirmed by agarose
gel electrophoresis with the characteristic appearance of a DNA streak in treated MCF7 cells indicating the ongoing apoptosis.
An erratum to this article can be found at 相似文献
93.
Nimisha Koodali Srikanth Krishnamoorthy Velayutham Dinesh Nandan Dharam Sankaralingam Shanmugam Nagarajan Muniyandi 《Molecular biology reports》2022,49(7):5963-5972
Molecular Biology Reports - Molecular studies on egg production in ducks were mostly focused on brain and ovaries as they are directly involved in egg production. Liver plays a vital role in... 相似文献
94.
Synthesis,Molecular Structure,and Chiroptical Properties of Dibenzylidene Derivatives of Bicyclo[3.3.1]nonane and Brexane 下载免费PDF全文
Synthesis of several enantiomerically pure unsaturated bicyclo[3.3.1]nonane and related brexane (tricyclo[4.3.0.03,7]nonane) derivatives bearing exocyclic benzylidene substituents from readily available (+)‐(1S,5S)‐bicyclo[3.3.1]nonane‐2,6‐dione was accomplished. Molecular geometry and chiroptical properties of compounds with enone and styrene chromophores were studied by X‐ray diffraction analysis, molecular modeling, and circular dichroism (CD) spectroscopy. Difunctional 3,7‐dibenzylidenebicyclo[3.3.1]nonanes, such as 2 and 7 , 8 , 9 , exhibited intense CD couplets, arising from the exciton coupling between the two unsaturated chromophores. The observed negative sign of the exciton couplets is congruent with the negative twist (negative chirality) defined by the two interacting transition dipoles. The sign of the Cotton effect corresponding to the π→π* transitions in the CD spectra of monoenone 4 and tricyclic brexane acetate 11 was correlated with the intrinsic dissymmetry (helicity) of the styrene chromophore. Chirality 27:728–737, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
95.
96.
Zhi Liu Esther C. Leng Kannan Gunasekaran Martin Pentony Min Shen Monique Howard Janelle Stoops Kathy Manchulenko Vladimir Razinkov Hua Liu William Fanslow Zhonghua Hu Nancy Sun Haruki Hasegawa Rutilio Clark Ian N. Foltz Wei Yan 《The Journal of biological chemistry》2015,290(12):7535-7562
Producing pure and well behaved bispecific antibodies (bsAbs) on a large scale for preclinical and clinical testing is a challenging task. Here, we describe a new strategy for making monovalent bispecific heterodimeric IgG antibodies in mammalian cells. We applied an electrostatic steering mechanism to engineer antibody light chain-heavy chain (LC-HC) interface residues in such a way that each LC strongly favors its cognate HC when two different HCs and two different LCs are co-expressed in the same cell to assemble a functional bispecific antibody. We produced heterodimeric IgGs from transiently and stably transfected mammalian cells. The engineered heterodimeric IgG molecules maintain the overall IgG structure with correct LC-HC pairings, bind to two different antigens with comparable affinity when compared with their parental antibodies, and retain the functionality of parental antibodies in biological assays. In addition, the bispecific heterodimeric IgG derived from anti-HER2 and anti-EGF receptor (EGFR) antibody was shown to induce a higher level of receptor internalization than the combination of two parental antibodies. Mouse xenograft BxPC-3, Panc-1, and Calu-3 human tumor models showed that the heterodimeric IgGs strongly inhibited tumor growth. The described approach can be used to generate tools from two pre-existent antibodies and explore the potential of bispecific antibodies. The asymmetrically engineered Fc variants for antibody-dependent cellular cytotoxicity enhancement could be embedded in monovalent bispecific heterodimeric IgG to make best-in-class therapeutic antibodies. 相似文献
97.
Elena M. Pugacheva Samuel Rivero-Hinojosa Celso A. Espinoza Claudia Fabiola Méndez-Catalá Sungyun Kang Teruhiko Suzuki Natsuki Kosaka-Suzuki Susan Robinson Vijayaraj Nagarajan Zhen Ye Abdelhalim Boukaba John E. J. Rasko Alexander V. Strunnikov Dmitri Loukinov Bing Ren Victor V. Lobanenkov 《Genome biology》2015,16(1)
98.
99.
Nagarajan G Tsai YJ Chen CY Chang CF 《The Journal of steroid biochemistry and molecular biology》2011,127(3-5):155-166
100.
The catalytic domain of epidermal growth factor receptor (EGFR) is activated by dimerization, which requires allosteric coupling between distal dimerization and catalytic sites. Although crystal structures of EGFR kinases, solved in various conformational states, have provided important insights into EGFR activation by dimerization, the atomic details of how dimerization signals are dynamically coupled to catalytic regions of the kinase core are not fully understood. In this study, we have performed unrestrained and targeted molecular dynamics simulations on the active and inactive states of EGFR, followed by principal component analysis on the simulated trajectories, to identify correlated motions in the EGFR kinase domain upon dimerization. Our analysis reveals that the conformational changes associated with the catalytic functions of the kinase core are highly correlated with motions in the juxtamembrane (JM) and C-terminal tail, two flexible structural elements that play an active role in EGFR kinase activation and dimerization. In particular, the opening and closing of the ATP binding lobe relative to the substrate binding lobe is highly correlated with motions in the JM and C-terminal tail, suggesting that ATP and substrate binding can be coordinated with dimerization through conformational changes in the JM and C-terminal tail. Our study pinpoints key residues involved in this conformational coupling, and provides new insights into the role of the JM and C-terminal tail segments in EGFR kinase functions. 相似文献