全文获取类型
收费全文 | 1962篇 |
免费 | 164篇 |
出版年
2023年 | 4篇 |
2022年 | 24篇 |
2021年 | 38篇 |
2020年 | 26篇 |
2019年 | 28篇 |
2018年 | 42篇 |
2017年 | 36篇 |
2016年 | 60篇 |
2015年 | 89篇 |
2014年 | 98篇 |
2013年 | 142篇 |
2012年 | 145篇 |
2011年 | 136篇 |
2010年 | 104篇 |
2009年 | 86篇 |
2008年 | 140篇 |
2007年 | 109篇 |
2006年 | 107篇 |
2005年 | 108篇 |
2004年 | 76篇 |
2003年 | 75篇 |
2002年 | 70篇 |
2001年 | 20篇 |
2000年 | 24篇 |
1999年 | 20篇 |
1998年 | 19篇 |
1997年 | 15篇 |
1996年 | 20篇 |
1995年 | 15篇 |
1994年 | 6篇 |
1993年 | 13篇 |
1992年 | 23篇 |
1991年 | 22篇 |
1990年 | 17篇 |
1989年 | 15篇 |
1988年 | 24篇 |
1987年 | 9篇 |
1986年 | 7篇 |
1985年 | 16篇 |
1984年 | 20篇 |
1983年 | 7篇 |
1982年 | 8篇 |
1981年 | 13篇 |
1980年 | 6篇 |
1979年 | 8篇 |
1978年 | 8篇 |
1977年 | 6篇 |
1974年 | 4篇 |
1969年 | 3篇 |
1967年 | 3篇 |
排序方式: 共有2126条查询结果,搜索用时 125 毫秒
91.
Giorgio Perin Alessandra Bellan Andrea Bernardi Fabrizio Bezzo Tomas Morosinotto 《Physiologia plantarum》2019,166(1):380-391
The massive increase in carbon dioxide concentration in the atmosphere driven by human activities is causing huge negative consequences and new sustainable sources of energy, food and materials are highly needed. Algae are unicellular photosynthetic microorganisms that can provide a highly strategic contribution to this challenge as alternative source of biomass to complement crops cultivation. Algae industrial cultures are commonly limited by light availability, and biomass accumulation is strongly dependent on their photon‐to‐biomass conversion efficiency. Investigation of algae photosynthetic metabolism is thus strategic for the generation of more efficient strains with higher productivity. Algae are cultivated at industrial scale in conditions highly different from the natural niches they adapted to and strains development efforts must fully consider the seminal influence on productivity of regulatory mechanism of photosynthesis as well as of cultivation parameters like cells concentration, light distribution in the culture, mixing, nutrients and carbon dioxide availability. In this review we will focus in particular on how mathematical models can account for the complex influence of all environmental parameters and can be exploited for development of improved algae strains. 相似文献
92.
L Mazzanti R A Rabini I Testa G V Coppa C Catassi M Cecconi P L Giorgi 《Biochemical medicine and metabolic biology》1991,45(2):181-187
Intracellular sodium concentration and Na+/K(+)-ATPase activity were studied in erythrocytes obtained from members of 14 families with one hypertensive parent and from age-matched control subjects, as part of a study on the genetic and environmental determinants of essential hypertension. We found reduced Na+/K(+)-ATPase activity, increased intracellular Na+ concentration, and reduced urinary Na+ excretion in hypertensive patients as compared with the control subjects. In the offspring of hypertensive parents an increase in intracellular Na+ concentration and a decrease in Na+/K(+)-ATPase activity were observed, with a significant correlation relating such parameters. Normotensive spouses did not differ from the normotensive control adults in any of the parameters studied, suggesting no influence of shared family environment in our family group. These data suggest that there is a strong genetic influence contributing to familiar alterations in cation transport, although long-term studies are needed to evaluate the influence of environmental determinants. 相似文献
93.
Ian P. Holmes Richard J. Blunt Olivier E. Lorthioir Stephen M. Blowers Andy Gribble Andrew H. Payne Ian G. Stansfield Martyn Wood Patrick M. Woollard Charlie Reavill Claire M. Howes Fabrizio Micheli Romano Di Fabio Daniele Donati Silvia Terreni Dieter Hamprecht Luca Arista Angela Worby Steve P. Watson 《Bioorganic & medicinal chemistry letters》2010,20(6):2013-2016
The identification of a highly selective D2 partial agonist, D3 antagonist tool molecule which demonstrates high levels of brain exposure and selectivity against an extensive range of dopamine, serotonin, adrenergic, histamine, and muscarinic receptors is described. 相似文献
94.
Rapid modification of bacterial artificial chromosomes by ET-recombination 总被引:53,自引:7,他引:46
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
We present a method to modify bacterial artificial chromosomes (BACs) resident in their host strain. The method is based on homologous recombination by ET-cloning. We have successfully modified BACs at two distinct loci by recombination with a PCR product containing homology arms of 50 nt. The procedure we describe here is rapid, was found to work with high efficiency and should be applicable to any BAC modification desired. 相似文献
95.
Definition of a short region of XPG necessary for TFIIH interaction and stable recruitment to sites of UV damage
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Thorel F Constantinou A Dunand-Sauthier I Nouspikel T Lalle P Raams A Jaspers NG Vermeulen W Shivji MK Wood RD Clarkson SG 《Molecular and cellular biology》2004,24(24):10670-10680
XPG is the human endonuclease that cuts 3' to DNA lesions during nucleotide excision repair. Missense mutations in XPG can lead to xeroderma pigmentosum (XP), whereas truncated or unstable XPG proteins cause Cockayne syndrome (CS), normally yielding life spans of <7 years. One XP-G individual who had advanced XP/CS symptoms at 28 years has been identified. The genetic, biochemical, and cellular defects in this remarkable case provide insight into the onset of XP and CS, and they reveal a previously unrecognized property of XPG. Both of this individual's XPG alleles produce a severely truncated protein, but an infrequent alternative splice generates an XPG protein lacking seven internal amino acids, which can account for his very slight cellular UV resistance. Deletion of XPG amino acids 225 to 231 does not abolish structure-specific endonuclease activity. Instead, this region is essential for interaction with TFIIH and for the stable recruitment of XPG to sites of local UV damage after the prior recruitment of TFIIH. These results define a new functional domain of XPG, and they demonstrate that recruitment of DNA repair proteins to sites of damage does not necessarily lead to productive repair reactions. This observation has potential implications that extend beyond nucleotide excision repair. 相似文献
96.
97.
Bismuto E Nucci R Febbraio F Tanfani F Gentile F Briante R Scirè A Bertoli E Amodeo P 《European biophysics journal : EBJ》2004,33(1):38-49
The perturbation induced by mono- and divalent cations on the thermophilicity and thermostability of Solfolobus solfataricus -glycosidase, a hyperthermophilic tetrameric enzyme, has been investigated by spectroscopic and computational simulation methods to ascertain the Hofmeister effects on two strategic protein regions identified previously. Specifically, (1) an extra segment (83–124), present only in the sequence of hyperthermophilic glycosidases and recognized as an important thermostability determinant for the enzyme structure; and (2) a restricted area of the subunit interface responsible for the quaternary structure maintenance. Mono- and divalent cations inhibit to a different extent the -glycosidase activity, whose kinetic constants show an apparent competitive inhibition of the catalytic process that reflects the Hofmeister order. The thermostability is also affected by the nature and charge of the cations, reaching maximal effects for the case of Mg2+. Fourier transform infrared spectroscopy has revealed very small changes in the protein secondary structure in the presence of the investigated cations at 20 °C, while large effects on the protein melting temperatures are observed. Computational analysis of the enzyme structure has identified negative patches on the accessible surface of the two identified regions. Following the Hofmeister series, cations weaken the existing electrostatic network that links the extra segment to the remaining protein matrix. In particular, the perturbing action of cations could involve the ionic pair interactions E107–R245 and E109–R185, thus leading to a local destructuring of the extra segment as a possible starting event for thermal destabilization. A detailed investigation of the electrostatic network at the A–C intermolecular interface of Sgly after energy minimization suggests that cations could cause a strong attenuation of the ion pair interactions E474–K72 and D473–R402, with consequent partial dissociation of the tetrameric structure.Abbreviations Amide I
amide I band in a 2H2O medium
- EM
energy minimization
- ONPG
o-nitrophenyl--d-galactopyranoside
- Sgly
Escherichia coli expressed Sulfolobus solfataricus -glycosidase 相似文献
98.
Acetylcholinesterase (AChE) inhibitors are currently the only approved therapy for the treatment of Alzheimer's disease, only a limited number of drugs are commercially available. A library of non-alkaloidal natural compounds was investigated. To this end, a convenient microtitre plate method for assaying AChE inhibition, which allows a complete kinetic analysis of AChE inhibitors, was developed. Seven active compounds with Ki values in the micromolar range were identified, six of which were xanthones. This is the first report that a promising potential for AChE inhibition exists in such non-nitrogenous natural compounds. Furthermore, four xanthones among these xanthones had already been described as monoamine oxidase (MAO) inhibitors, making then dual AChE/MAO inhibitors of great interest. 相似文献
99.
The two-faced nature of protozoa allowed us to study the relationship between cell cycle and behaviour in Euplotes crassus; the former represents one of the most typical cellular traits, the latter is one of the most significant characteristics of an organism. Dividing cells of E. crassus were isolated on a slide and recorded for 11 h: the classic ethographic parameters were calculated every 60 min. The percentage of mobile cells went from 0-100% in the first 2.5 h. This value was maintained for 6.5 h, but from 9 h the value began to drop, reaching 0% at 11 h. The relative frequency of leftward arcs was very high in the first hour, the radius and length of the arcs increased from 1-7 h; velocity showed a similar trend, peaking at 7 h. All our results showed that the behaviour of this ciliate is heavily affected by its cell-division cycle. 相似文献
100.
Carnevali S Petruzzelli S Longoni B Vanacore R Barale R Cipollini M Scatena F Paggiaro P Celi A Giuntini C 《American journal of physiology. Lung cellular and molecular physiology》2003,284(6):L955-L963
Cigarette smoke is a mixture of chemicals having direct and/or indirect toxic effects on different lung cells. We investigated the effect of cigarette smoke on human lung fibroblasts (HFL-1) oxidation and apoptosis. Cells were exposed to various concentrations (1, 5, and 10%) of cigarette smoke extract (CSE) for 3 h, and oxidative stress and apoptosis were assessed by fluorescence-activated cell sorting and confocal laser fluorescence microscopy. Both oxidative stress and apoptosis exhibited a dose-response relationship with CSE concentrations. Lung fibroblasts also showed marked DNA fragmentation at the Comet assay after exposure to 10% CSE. Coincubation of HLF-1 cells with N-acetylcysteine (1 mM) during CSE exposure significantly reduced oxidative stress, apoptosis, and DNA fragmentation, whereas preincubation (3 h) with the glutathione-depleting agent buthionine sulfoximine (125 microM) produced a significant increase of oxidative stress. Cigarette smoke is a potent source of oxidative stress, DNA damage, and apoptosis for HFL-1 cells, and we speculate that this could contribute to the development of pulmonary emphysema in the lungs of smokers. 相似文献