全文获取类型
收费全文 | 621篇 |
免费 | 39篇 |
国内免费 | 9篇 |
出版年
2023年 | 8篇 |
2022年 | 16篇 |
2021年 | 25篇 |
2020年 | 13篇 |
2019年 | 16篇 |
2018年 | 19篇 |
2017年 | 21篇 |
2016年 | 14篇 |
2015年 | 23篇 |
2014年 | 30篇 |
2013年 | 33篇 |
2012年 | 22篇 |
2011年 | 18篇 |
2010年 | 20篇 |
2009年 | 19篇 |
2008年 | 18篇 |
2007年 | 24篇 |
2006年 | 20篇 |
2005年 | 24篇 |
2004年 | 18篇 |
2003年 | 13篇 |
2002年 | 22篇 |
2001年 | 22篇 |
2000年 | 14篇 |
1999年 | 15篇 |
1998年 | 16篇 |
1997年 | 11篇 |
1996年 | 10篇 |
1995年 | 11篇 |
1994年 | 12篇 |
1993年 | 13篇 |
1992年 | 12篇 |
1991年 | 16篇 |
1990年 | 12篇 |
1989年 | 5篇 |
1988年 | 7篇 |
1987年 | 14篇 |
1986年 | 4篇 |
1985年 | 7篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1982年 | 7篇 |
1981年 | 4篇 |
1980年 | 5篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1976年 | 3篇 |
排序方式: 共有669条查询结果,搜索用时 15 毫秒
31.
The tubulin molecule consists of an - and a β-subunit, each of which exists in several isotypic forms. It has been previously shown that one of the isotypes of neuroblastoma β-tubulin is phosphorylated at a serine residue in vivo [(1985) J. Cell Biol. 100, 764–774]. Here we identify the phosphorylated isotype as β2 (type III). Moreover, the large size of the phosphorylated tryptic peptide and sequence comparisons of vertebrate β-tubulins suggest that one of the two serines in positions 444 and 446 is the phosphorylated residue. Our results raise the possibility that β2-tubulin differs functionally from the other β-tubulin isotypes. 相似文献
32.
Zehua Zhou Yabing Duan Jie Zhang Fei Lu Yuanye Zhu Won Bo Shim Mingguo Zhou 《Molecular Plant Pathology》2021,22(2):163-174
In Fusarium graminearum, a trichothecene biosynthetic complex known as the toxisome forms ovoid and spherical structures in the remodelled endoplasmic reticulum (ER) under mycotoxin-inducing conditions. Previous studies also demonstrated that disruption of actin and tubulin results in a significant decrease in deoxynivalenol (DON) biosynthesis in F. graminearum. However, the functional association between the toxisome and microtubule components has not been clearly defined. In this study we tested the hypothesis that the microtubule network provides key support for toxisome assembly and thus facilitates DON biosynthesis. Through fluorescent live cell imaging, knockout mutant generation, and protein–protein interaction assays, we determined that two of the four F. graminearum tubulins, α1 and β2 tubulins, are indispensable for DON production. We also showed that these two tubulins are directly associated. When the α1–β2 tubulin heterodimer is disrupted, the metabolic activity of the toxisome is significantly suppressed, which leads to significant DON biosynthesis impairment. Similar phenotypic outcomes were shown when F. graminearum wild type was treated with carbendazim, a fungicide that binds to microtubules and disrupts spindle formation. Based on our results, we propose a model where α1–β2 tubulin heterodimer serves as the scaffold for functional toxisome assembly in F. graminearum. 相似文献
33.
34.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):421-429
A theoretical study on the binding conformations and the quantitative structure–activity relationship (QSAR) of combretastatin A4 (CA-4) analogs as inhibitors toward tubulin has been carried out using docking analysis and comparative molecular field analysis (CoMFA). The appropriate binding orientations and conformations of these compounds interacting with tubulin were revealed by the docking study; and a 3D-QSAR model showing significant statistical quality and satisfactory predictive ability was established, in which the correlation coefficient (R2) and cross-validation coefficient (q2) were 0.955 and 0.66, respectively. The same model was further applied to predict the pIC50 values for 16 congeneric compounds as external test set, and the predictive correlation coefficient R2pred reached 0.883. Other tests on additional validations further confirmed the satisfactory predictive power of the model. In this work, it was very interesting to find that the 3D topology structure of the active site of tubulin from the docking analysis was in good agreement with the 3D-QSAR model from CoMFA for this series of compounds. Some key structural factors of the compounds responsible for cytotoxicity were reasonably presented. These theoretical results can offer useful references for understanding the action mechanism and directing the molecular design of this kind of inhibitor with improved activity. 相似文献
35.
Shima Rajaei Saeed Karima Hessam Sepasi Tehrani Somayeh Shateri Somayeh Mahmoodi Baram Meisam Mahdavi Farzad Mokhtari Alimohammad Alimohammadi Abbas Tafakhori Abolfazl Amiri Vajiheh Aghamollaii Hamid Fatemi Masoumeh Rajabibazl Farzad Kobarfard Ali Gorji 《Journal of neurochemistry》2020,155(2):207-224
36.
37.
Wen‐Yao Kong Xiao‐Feng Chen Jing Shi Shahla Karim Baloch Jin‐Liang Qi Hai‐Liang Zhu Xiao‐Ming Wang Yong‐Hua Yang 《Chirality》2013,25(11):757-762
A series of shikonin derivatives, selectively acylated by various fluorinated carboxylic acids at the side chain of shikonin, were synthesized and their anticancer activity evaluated, in which eight compounds are reported for the first time. Among all the compounds tested, compound S7 showed the most potent anticancer activity against B16‐F10 (malignant melanoma cells), MG63 (human osteosarcoma cells), and A549 (lung cancer cells) with IC50 0.39 ± 0.01, 0.72 ± 0.04 and 0.58 ± 0.02 µmol/L. Docking simulation of compound S7 was carried out to position S7 into a tubulin active site to determine the probable binding conformation. All the results suggested that compound S7 may be a potential anticancer agent. Chirality 25:757–762, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
38.
Shaoming Chi Wei Xie Jiwei Zhang 《Journal of biomolecular structure & dynamics》2013,31(10):2234-2254
Vinblastine (VLB) is one of vinca alkaloids with high cytotoxicity toward cancer cells approved for clinical use. However, because of drug resistance, toxicity, and other side effects caused from the use of VLB, new vinca alkaloids with higher cytotoxicity toward cancer cells and other good qualities need to develop. One strategy is to further study and better understand the essence why VLB possesses the high cytotoxicity toward cancer cells. In present work, by using molecular simulation, molecular docking, density functional calculation, and the crystal structure of α,β-tubulin complex, we find two modes labeled in catharanthine moiety (CM) and vindoline moiety (VM) modes of VLB bound with the interface of α,β-tubulin to probe the essence why VLB has the high cytotoxicity toward cancer cells. In the CM mode, nine key residues B-Ser178, B-Asp179, B-Glu183, B-Tyr210, B-Asp226, C-Lys326, C-Asp327, C-Lys336, and C-Lys352 from the α,β-tubulin complex are determined as the active sites for the interaction of VLB with α,β-tubulin. Some of them such as B-Ser178, B-Glu183, B-Tyr210, B-Asp226, C-Lys326, C-Asp327, and C-Lys336 are newly identified as the active sites in present work. The affinity between VLB and the active pocket within the interface of α,β-tubulin is ?60.8 kJ mol?1 in the CM mode. In the VM mode, that is a new mode established in present paper, nine similar key residues B-Lys176, B-Ser178, B-Asp179, B-Glu183, B-Tyr210, B-Asp226, C-Lys326, C-Asp327, and C-Lys336 from the α,β-tubulin complex are found as the active sites for the interaction with VLB. The difference is from one key residue C-Lys352 in the CM mode changed to the key residue B-Lys176 in the VM mode. The affinity between VLB and the active pocket within the interface of α,β-tubulin is ?96.3 kJ mol?1 in the VM mode. Based on the results obtained in present work, and because VLB looks like two faces, composed of CM and VM both to have similar polar active groups, to interact with the active sites, we suggest double-faces sticking mechanism for the binding of VLB to the interface of α,β-tubulin. The double-faces sticking mechanism can be used to qualitatively explain high cytotoxicity toward cancer cells of vinca alkaloids including vinblastine, vincristine, vindestine, and vinorelbine approved for clinical use and vinflunine still in a phase III clinical trial. Furthermore, this mechanism will be applied to develop novel vinca alkaloids with much higher cytotoxicity toward cancer cells. 相似文献
39.
40.
Morphological,Molecular and Pathological Characterization of Phytophthora amaranthi sp. nov. from Amaranth in Taiwan
下载免费PDF全文
![点击此处可从《Journal of Phytopathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Pao‐Jen Ann Jin‐Hsin Huang Jyh‐Nong Tsai Wen‐Hsiung Ko 《Journal of Phytopathology》2016,164(2):94-101
In the spring of 2007, a serious disease on amaranth was noticed in several farms in the major amaranth production area in central Taiwan. Abundant oospores were found in the disease tissues. A species of Phytophthora was consistently isolated from disease tissues. The organism formed abundant oospores with smooth walls and with amphigynous antheridia in single culture. Sporangia were partially deciduous with short‐ to medium‐length pedicels. Morphological characteristics of this organism did not match any reported Phytophthora species, and the organism was named Phytophthora amaranthi. Pathogenicity tests and molecular characterization confirmed the identity of the organism as a new pathogen of amaranth and a new species of Phytophthora. 相似文献