全文获取类型
收费全文 | 4773篇 |
免费 | 478篇 |
国内免费 | 498篇 |
专业分类
5749篇 |
出版年
2024年 | 26篇 |
2023年 | 190篇 |
2022年 | 223篇 |
2021年 | 273篇 |
2020年 | 238篇 |
2019年 | 276篇 |
2018年 | 240篇 |
2017年 | 204篇 |
2016年 | 231篇 |
2015年 | 238篇 |
2014年 | 275篇 |
2013年 | 398篇 |
2012年 | 211篇 |
2011年 | 218篇 |
2010年 | 210篇 |
2009年 | 238篇 |
2008年 | 233篇 |
2007年 | 235篇 |
2006年 | 235篇 |
2005年 | 218篇 |
2004年 | 168篇 |
2003年 | 165篇 |
2002年 | 118篇 |
2001年 | 84篇 |
2000年 | 69篇 |
1999年 | 55篇 |
1998年 | 44篇 |
1997年 | 44篇 |
1996年 | 43篇 |
1995年 | 48篇 |
1994年 | 48篇 |
1993年 | 25篇 |
1992年 | 20篇 |
1991年 | 33篇 |
1990年 | 19篇 |
1989年 | 13篇 |
1988年 | 10篇 |
1987年 | 18篇 |
1986年 | 9篇 |
1985年 | 12篇 |
1984年 | 10篇 |
1983年 | 6篇 |
1982年 | 12篇 |
1981年 | 15篇 |
1980年 | 8篇 |
1979年 | 7篇 |
1977年 | 4篇 |
1976年 | 11篇 |
1975年 | 9篇 |
1974年 | 4篇 |
排序方式: 共有5749条查询结果,搜索用时 15 毫秒
991.
莽草酸是大肠杆菌合成芳香族氨基酸的中间代谢物,也是抗流感药物"达菲"的重要合成前体。合成莽草酸需要截断莽草酸途径,导致芳香族氨基酸无法合成,因此面临细胞生长受到抑制的问题。使用动态调控策略通过将细胞生长和莽草酸的合成相互分离,可以提高菌株的生产性能。通过使用生长偶联型启动子和降解决定子(Degrons),组建动态分子开关。利用该动态分子开关实现细胞生长与莽草酸合成分离,在5L发酵罐中经过72h发酵得到了14.33g/L的莽草酸。结果表明,这种动态分子开关可以通过调控靶蛋白丰度来改变碳流量平衡,使菌株获得更优秀的生产性能。 相似文献
992.
993.
Variability in metabolic scaling in animals, the relationship between metabolic rate (R) and body mass (M), has been a source of debate and controversy for decades. R is proportional to Mb, the precise value of b much debated, but historically considered equal in all organisms. Recent metabolic theory, however, predicts b to vary among species with ecology and metabolic level, and may also vary within species under different abiotic conditions. Under climate change, most species will experience increased temperatures, and marine organisms will experience the additional stressor of decreased seawater pH (‘ocean acidification’). Responses to these environmental changes are modulated by myriad species-specific factors. Body-size is a fundamental biological parameter, but its modulating role is relatively unexplored. Here, we show that changes to metabolic scaling reveal asymmetric responses to stressors across body-size ranges; b is systematically decreased under increasing temperature in three grazing molluscs, indicating smaller individuals were more responsive to warming. Larger individuals were, however, more responsive to reduced seawater pH in low temperatures. These alterations to the allometry of metabolism highlight abiotic control of metabolic scaling, and indicate that responses to climate warming and ocean acidification may be modulated by body-size. 相似文献
994.
Nico M. van Gelder 《Neurochemical research》1987,12(2):111-119
Epilepsy is an ancient disorder which treatment over the centuries has been guided by preconceptions regarding its origin. The major improvements in epilepsy management came following the discovery of the EEG and the development of seizure suppressing agents. These advances in diagnosis and anticonvulsant therapy have further ingrained the conviction that epilepsy is a disease of neurons. Evidence presented here is intended to support a different point of view which suggests that the metabolic modifications in epileptogenic tissue denote subtle alterations in the anatomical and biochemical relationship between neurons and their glial envelopes. As a result the extracellular environment of these cells contain higher than normal levels of glutamic acid. This creates an unnatural functional connectivity between neurons so that they establish abnormal synchronous activity between them and become hyperexcitable due to the depolarizing milieu. To compensate for these biochemical changes it is suggested that some thought might be given to epilepsy management by metabolic manipulation. The measures should be directed specifically towards improving the ability of glia to remove glutamic acid from the extracellular milieu. Two obvious possibilities are to enhance glial glutamine synthesis and to improve the interstitial wash-out of glutamic acid in epileptogenic epicenters. Such a therapy would anticipate to gradually diminish seizure incidence and susceptibility without, however, having a direct action on convulsive episodes per se. The approach must be considered an adjunct to current epilepsy treatment and not a substitute for the use of anticonvulsants.Special Issue Dedicated to Dr. Abel Lajtha. 相似文献
995.
Yunhe Meng Xixi Shao Yan Wang Yumei Li Xiaojian Zheng Gongyuan Wei Seon-Won Kim Chonglong Wang 《Biotechnology and bioengineering》2020,117(11):3499-3507
Squalene is a lipophilic and non-volatile triterpene with many industrial applications for food, pharmaceuticals, and cosmetics. Metabolic engineering focused on optimization of the production pathway suffer from little success in improving titers because of a limited space of the cell membrane accommodating the lipophilic product. Extension of cell membrane would be a promising approach to overcome the storage limitation for successful production of squalene. In this study, Escherichia coli was engineered for squalene production by overexpression of some membrane proteins. The highest production of 612 mg/L was observed in the engineered E. coli with overexpression of Tsr, a serine chemoreceptor protein, which induced invagination of inner membrane to form multilayered structure. It was also observed an increase in unsaturated fatty acid in membrane lipids composition, suggesting cellular response to maintain membrane fluidity against squalene accumulation in the engineered strain. This study potentiates the capability of E. coli for squalene production and provides an effective strategy for the enhanced production of such compounds. 相似文献
996.
Xiangming Li Yujian Zhang Li Jing Zongming Fu Ou Ma Jishna Ganguly Nilesh Vaidya Richard Sisson Jennifer Naginskaya Avinash Chinthala Minggang Cui Ryan Yamagata Mark Wilson Matthew Sanders Zihao Wang Paola Lo Surdo Marcin Bugno 《Biotechnology progress》2020,36(2):e2914
Mammalian cell line generation typically includes stable pool generation, single cell cloning and several rounds of clone selection based on cell growth, productivity and product quality criteria. Individual clone expansion and phenotype-based ranking is performed initially for hundreds or thousands of mini-scale cultures, representing the major operational challenge during cell line development. Automated cell culture and analytics systems have been developed to enable high complexity clone selection workflows; while ensuring traceability, safety, and quality of cell lines intended for biopharmaceutical applications. Here we show that comprehensive and quantitative assessment of cell growth, productivity, and product quality attributes are feasible at the 200–1,200 cell colony stage, within 14 days of the single cell cloning in static 96-well plate culture. The early cell line characterization performed prior to the clone expansion in suspension culture can be used for a single-step, direct selection of high quality clones. Such clones were comparable, both in terms of productivity and critical quality attributes (CQAs), to the top-ranked clones identified using an established iterative clone screening approach. Using a complex, multi-subunit antigen as a model protein, we observed stable CQA profiles independently of the cell culture format during the clonal expansion as well as in the batch and fed-batch processes. In conclusion, we propose an accelerated clone selection approach that can be readily incorporated into various cell line development workstreams, leading to significant reduction of the project timelines and resource requirements. 相似文献
997.
998.
999.
人类活动造成大气二氧化碳(CO2)浓度不断升高,使当今世界面临着气候变化的重大危机。微生物CO2固定为实现地球“碳中和”提供了一条有前景的绿色发展路线。与自养微生物相比,异养微生物具有更快的生长速度和更先进的遗传工具,但是其固定CO2的能力还很有限。近年来,基于合成生物学技术强化异养微生物CO2固定受到诸多关注,主要包括优化能量供给、改造羧化途径以及基于异养微生物间接固定CO2。本综述将围绕上述3个方面重点讨论异养微生物CO2固定的研究进展,为将来更好地利用微生物CO2固定技术实现“碳达峰、碳中和”提供参考。 相似文献
1000.