全文获取类型
收费全文 | 468篇 |
免费 | 29篇 |
出版年
2023年 | 7篇 |
2022年 | 6篇 |
2021年 | 12篇 |
2020年 | 5篇 |
2019年 | 4篇 |
2018年 | 10篇 |
2017年 | 6篇 |
2016年 | 23篇 |
2015年 | 21篇 |
2014年 | 17篇 |
2013年 | 28篇 |
2012年 | 41篇 |
2011年 | 39篇 |
2010年 | 18篇 |
2009年 | 16篇 |
2008年 | 18篇 |
2007年 | 28篇 |
2006年 | 10篇 |
2005年 | 25篇 |
2004年 | 19篇 |
2003年 | 16篇 |
2002年 | 12篇 |
2001年 | 4篇 |
2000年 | 10篇 |
1999年 | 9篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 5篇 |
1988年 | 2篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 5篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 6篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1972年 | 2篇 |
1968年 | 2篇 |
1967年 | 2篇 |
1965年 | 3篇 |
1964年 | 2篇 |
排序方式: 共有497条查询结果,搜索用时 0 毫秒
491.
Increased antibacterial resistance (ABR) and limited drug discovery warrant optimized use of available antibiotics. One option is to rationally combine two antibiotics (fixed dose combination (FDC)) that may delay or prevent emergence of ABR in notorious pathogen. Major concern with FDC is the mutual interaction of its components that might influence their pharmacokinetic (PK) profile, requiring reassessing of whole formulation (adding cost and time). The interaction can be identified by comparing PK profile of a drug present in FDC with its independent entity. An open-label, crossover, single-dose comparative PK study of FDC (ceftriaxone and sulbactam) with their individual reference formulations was performed in 24 healthy adult subjects. No mutual PK interactions between ceftriaxone and sulbactam were observed. Pharmacokinetic data was used to develop a population-PK model to understand between-subject variability (BSV). Pharmacokinetics of ceftriaxone/sulbactam was explained by one and two compartment models, respectively. The subject’s “weight” was identified as a covariate explaining BSV. Both internal and external validations (healthy/infected subjects) were done. The model-derived population-PK parameters of FDC’s active components in infected subjects were similar to literature reported values of individual components. Efficacies of various FDC dosage regimens over a range of minimum inhibitory concentrations (MICs) were assessed by Monte Carlo simulations using population-PK parameters of infected/healthy subjects. In infected subjects, 3 g FDC/24 h can treat bacteria with MIC ≤8 μg/mL, while for MIC 8–32 μg/mL, 3 g FDC/12 h is recommended. Lastly, the developed population-PK model was successfully used to predict drug exposure in pediatric population. 相似文献
492.
Gopal K. Khuller Kasinathan Chinnaswamy Reeta Taneja Nalini Penumarti Vinay S. Bansal 《Current microbiology》1982,7(1):49-51
Enzymes of phospholipid synthesis were studied inMycobacterium smegmatis ATCC 607 grown at 37 and 27°C. The synthesis seemed to be regulated, at least partly, at the phosphatidic acid level by the specificity of the acyltransferases. The individual phospholipid species were found to be regulated at the enzymatic level in the maintenance of membrane fluidity. 相似文献
493.
Sheetal Uppal Shikha Salhotra Nitika Mukhi Fatima Kamal Zaidi Manas Seal Somdatta Ghosh Dey Rajiv Bhat Suman Kundu 《The Journal of biological chemistry》2015,290(4):1979-1993
Heme proteins, which reversibly bind oxygen and display a particular fold originally identified in myoglobin (Mb), characterize the “hemoglobin (Hb) superfamily.” The long known and widely investigated Hb superfamily, however, has been enriched by the discovery and investigation of new classes and members. Truncated Hbs typify such novel classes and exhibit a distinct two-on-two α-helical fold. The truncated Hb from the freshwater cyanobacterium Synechocystis exhibits hexacoordinate heme chemistry and bears an unusual covalent bond between the nonaxial His117 and a heme porphyrin 2-vinyl atom, which remains tightly associated with the globin unlike any other. It seems to be the most stable Hb known to date, and His117 is the dominant force holding the heme. Mutations of amino acid residues in the vicinity did not influence this covalent linkage. Introduction of a nonaxial His into sperm whale Mb at the topologically equivalent position and in close proximity to vinyl group significantly increased the heme stability of this prototype globin. Reversed phase chromatography, electrospray ionization-MS, and MALDI-TOF analyses confirmed the presence of covalent linkage in Mb I107H. The Mb mutant with the engineered covalent linkage was stable to denaturants and exhibited ligand binding and auto-oxidation rates similar to the wild type protein. This indeed is a novel finding and provides a new perspective to the evolution of Hbs. The successful attempt at engineering heme stability holds promise for the production of stable Hb-based blood substitute. 相似文献
494.
495.
‘Prevention is better than cure, especially when something has no cure.’ Cancer, in most patients is detected at the stage beyond which it becomes noncurative. Therefore, the early detection of cancer cells can play a crucial role in enhancing the chances of a patient's survival. In this light, we present a nonfluorescent receptor used for the detection of Zn2+ ion in MDA-MB-231 carcinoma cells that exhibits fluorescence turn-on behaviour upon binding with the metal ion. In this work, the synthesis of 11,16-bis(2,6-difluorobenzene)-6,6,21,21-tetramethyl-meta-benziporpho-6,21-dimethene and its Zn2+ chloride complex have been reported. The compounds were fully characterized using UV–visible, nuclear magnetic resonance (NMR), infrared (IR) and mass spectrometry. Furthermore, the X-ray polymorphs of a meta-benziporphodimethene analogue were added. The study of its bioimaging applications in MDA-MB-231 breast cancer cells for the detection of Zn2+ ions is reported. 相似文献
496.
Cohesin is a conserved chromatin-binding multisubunit protein complex involved in diverse chromosomal transactions such as sister-chromatid cohesion, chromosome condensation, regulation of gene expression, DNA replication, and repair. While working with a budding yeast temperature-sensitive mutant, mcd1-1, defective in a cohesin subunit, we observed that it was resistant to zymolyase, indicating an altered cell wall organization. The budding yeast cell wall is a strong but elastic structure essential for maintenance of cell shape and protection from extreme environmental challenges. Here, we show that the cohesin complex plays an important role in cell wall maintenance. Cohesin mutants showed high chitin content in the cell wall and sensitivity to multiple cell wall stress-inducing agents. Interestingly, temperature-dependent lethality of cohesin mutants was osmoremedial, in a HOG1-MAPK pathway-dependent manner, suggesting that the temperature sensitivity of these mutants may arise partially from cell wall defects. Moreover, Mpk1 hyper-phosphorylation indicated activation of the cell wall integrity (CWI) signaling pathway in cohesin mutants. Genetic interaction analysis revealed that the CWI pathway is essential for survival of mcd1-1 upon additional cell wall stress. The cell wall defect was independent of the cohesion function and accompanied by misregulation of expression of several genes having cell wall-related functions. Our findings reveal a requirement of cohesin in maintenance of CWI that is independent of the CWI pathway, and that may arise from cohesin’s role in regulating the expression of multiple genes encoding proteins involved in cell wall organization and biosynthesis. 相似文献
497.