全文获取类型
收费全文 | 1184篇 |
免费 | 103篇 |
国内免费 | 1篇 |
出版年
2023年 | 5篇 |
2022年 | 6篇 |
2021年 | 42篇 |
2020年 | 15篇 |
2019年 | 24篇 |
2018年 | 31篇 |
2017年 | 28篇 |
2016年 | 53篇 |
2015年 | 83篇 |
2014年 | 87篇 |
2013年 | 89篇 |
2012年 | 136篇 |
2011年 | 110篇 |
2010年 | 72篇 |
2009年 | 50篇 |
2008年 | 71篇 |
2007年 | 60篇 |
2006年 | 61篇 |
2005年 | 39篇 |
2004年 | 54篇 |
2003年 | 41篇 |
2002年 | 34篇 |
2001年 | 9篇 |
2000年 | 5篇 |
1999年 | 10篇 |
1998年 | 9篇 |
1997年 | 6篇 |
1995年 | 2篇 |
1994年 | 6篇 |
1992年 | 4篇 |
1991年 | 5篇 |
1989年 | 4篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1981年 | 5篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1972年 | 2篇 |
1966年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有1288条查询结果,搜索用时 78 毫秒
71.
I El Menyawi S Looareesuwan S Knapp F Thalhammer B Stoiser H Burgmann 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1998,706(2):2373
Previous studies have reported increased serum concentrations of nitrite/nitrate – the degradation products of nitric oxide – in Plasmodium vivax malaria and uncomplicated Plasmodium falciparum malaria. In all these studies, however, nitrite/nitrate has been measured spectrometrically using Griess reagent which carries major disadvantages in the determination of serum nitrite/nitrate. The method does not allow an exact differentiation of nitrite and biogenic amines that are physiologically present in plasma. In the present study we introduce high-performance liquid chromatography as a new, accurate and cost effective method for determination of serum nitrite/nitrate levels. Significantly increased nitrate concentrations were found in malaria patients and serum values remained above normal levels for at least 21 days. It could be shown that our HPLC method is a sensitive and cost-effective method for direct determination of nitrite/nitrate in serum samples, which is not influenced by the presence of biogenic amines. 相似文献
72.
Sabrina Klix Antje Els Katharina Paul Andreas Graessl Celal Oezerdem Oliver Weinberger Lukas Winter Christof Thalhammer Till Huelnhagen Jan Rieger Heidrun Mehling Jeanette Schulz-Menger Thoralf Niendorf 《PloS one》2015,10(1)
Purpose
This study examines the subjective acceptance during UHF-CMR in a cohort of healthy volunteers who underwent a cardiac MR examination at 7.0T.Methods
Within a period of two-and-a-half years (January 2012 to June 2014) a total of 165 healthy volunteers (41 female, 124 male) without any known history of cardiac disease underwent UHF-CMR. For the assessment of the subjective acceptance a questionnaire was used to examine the participants experience prior, during and after the UHF-CMR examination. For this purpose, subjects were asked to respond to the questionnaire in an exit interview held immediately after the completion of the UHF-CMR examination under supervision of a study nurse to ensure accurate understanding of the questions. All questions were answered with “yes” or “no” including space for additional comments.Results
Transient muscular contraction was documented in 12.7% of the questionnaires. Muscular contraction was reported to occur only during periods of scanning with the magnetic field gradients being rapidly switched. Dizziness during the study was reported by 12.7% of the subjects. Taste of metal was reported by 10.1% of the study population. Light flashes were reported by 3.6% of the entire cohort. 13% of the subjects reported side effects/observations which were not explicitly listed in the questionnaire but covered by the question about other side effects. No severe side effects as vomiting or syncope after scanning occurred. No increase in heart rate was observed during the UHF-CMR exam versus the baseline clinical examination.Conclusions
This study adds to the literature by detailing the subjective acceptance of cardiovascular magnetic resonance imaging examinations at a magnetic field strength of 7.0T. Cardiac MR examinations at 7.0T are well tolerated by healthy subjects. Broader observational and multi-center studies including patient cohorts with cardiac diseases are required to gain further insights into the subjective acceptance of UHF-CMR examinations. 相似文献73.
Ole A. Andreassen Rahul S. Desikan Yunpeng Wang Wesley K. Thompson Andrew J. Schork Verena Zuber Nadezhda T. Doncheva Eva Ellinghaus Mario Albrecht Morten Mattingsdal Andre Franke Benedicte A. Lie Ian G. Mills P?l Aukrust Linda K. McEvoy Srdjan Djurovic Tom H. Karlsen Anders M. Dale 《PloS one》2015,10(5)
74.
75.
Petr Rada Abhijith Radhakrishna Makki Verena Zimorski Sriram Garg Vladimír Hampl Ivan Hrdy Sven B. Gould Jan Tachezy 《Eukaryotic cell》2015,14(12):1264-1275
Mitochondrial evolution entailed the origin of protein import machinery that allows nuclear-encoded proteins to be targeted to the organelle, as well as the origin of cleavable N-terminal targeting sequences (NTS) that allow efficient sorting and import of matrix proteins. In hydrogenosomes and mitosomes, reduced forms of mitochondria with reduced proteomes, NTS-independent targeting of matrix proteins is known. Here, we studied the cellular localization of two glycolytic enzymes in the anaerobic pathogen Trichomonas vaginalis: PPi-dependent phosphofructokinase (TvPPi-PFK), which is the main glycolytic PFK activity of the protist, and ATP-dependent PFK (TvATP-PFK), the function of which is less clear. TvPPi-PFK was detected predominantly in the cytosol, as expected, while all four TvATP-PFK paralogues were imported into T. vaginalis hydrogenosomes, although none of them possesses an NTS. The heterologous expression of TvATP-PFK in Saccharomyces cerevisiae revealed an intrinsic capability of the protein to be recognized and imported into yeast mitochondria, whereas yeast ATP-PFK resides in the cytosol. TvATP-PFK consists of only a catalytic domain, similarly to “short” bacterial enzymes, while ScATP-PFK includes an N-terminal extension, a catalytic domain, and a C-terminal regulatory domain. Expression of the catalytic domain of ScATP-PFK and short Escherichia coli ATP-PFK in T. vaginalis resulted in their partial delivery to hydrogenosomes. These results indicate that TvATP-PFK and the homologous ATP-PFKs possess internal structural targeting information that is recognized by the hydrogenosomal import machinery. From an evolutionary perspective, the predisposition of ancient ATP-PFK to be recognized and imported into hydrogenosomes might be a relict from the early phases of organelle evolution. 相似文献
76.
Carrie J. Finno Carlynn Stevens Amy Young Verena Affolter Nikhil A. Joshi Sheila Ramsay Danika L. Bannasch 《PLoS genetics》2015,11(4)
Horses belong to the order Perissodactyla and bear the majority of their weight on their third toe; therefore, tremendous force is applied to each hoof. An inherited disease characterized by a phenotype restricted to the dorsal hoof wall was identified in the Connemara pony. Hoof wall separation disease (HWSD) manifests clinically as separation of the dorsal hoof wall along the weight-bearing surface of the hoof during the first year of life. Parents of affected ponies appeared clinically normal, suggesting an autosomal recessive mode of inheritance. A case-control allelic genome wide association analysis was performed (ncases = 15, ncontrols = 24). Population stratification (λ = 1.48) was successfully improved by removing outliers (ncontrols = 7) identified on a multidimensional scaling plot. A genome-wide significant association was detected on chromosome 8 (praw = 1.37x10-10, pgenome = 1.92x10-5). A homozygous region identified in affected ponies spanned from 79,936,024-81,676,900 bp and contained a family of 13 annotated SERPINB genes. Whole genome next-generation sequencing at 6x coverage of two cases and two controls revealed 9,758 SNVs and 1,230 indels within the ~1.7-Mb haplotype, of which 17 and 5, respectively, segregated with the disease and were located within or adjacent to genes. Additional genotyping of these 22 putative functional variants in 369 Connemara ponies (ncases = 23, ncontrols = 346) and 169 horses of other breeds revealed segregation of three putative variants adjacent or within four SERPIN genes. Two of the variants were non-coding and one was an insertion within SERPINB11 that introduced a frameshift resulting in a premature stop codon. Evaluation of mRNA levels at the proximal hoof capsule (ncases = 4, ncontrols = 4) revealed that SERPINB11 expression was significantly reduced in affected ponies (p<0.001). Carrier frequency was estimated at 14.8%. This study describes the first genetic variant associated with a hoof wall specific phenotype and suggests a role of SERPINB11 in maintaining hoof wall structure. 相似文献
77.
78.
Verena Leder Martina Lummer Kathrin Tegeler Fabian Humpert Martin Lewinski Mark Schüttpelz Dorothee Staiger 《Biochemical and biophysical research communications》2014
Arabidopsis thaliana glycine-rich RNA binding protein 7 (AtGRP7) is part of a negative feedback loop through which it regulates alternative splicing and steady-state abundance of its pre-mRNA. Here we use fluorescence correlation spectroscopy to investigate the requirements for AtGRP7 binding to its intron using fluorescently-labelled synthetic oligonucleotides. By systematically introducing point mutations we identify three nucleotides that lead to an increased Kd value when mutated and thus are critical for AtGRP7 binding. Simultaneous mutation of all three residues abrogates binding. The paralogue AtGRP8 binds to an overlapping motif but with a different sequence preference, in line with overlapping but not identical functions of this protein pair. Truncation of the glycine-rich domain reduces the binding affinity of AtGRP7, showing for the first time that the glycine-rich stretch of a plant hnRNP-like protein contributes to binding. Mutation of the conserved R49 that is crucial for AtGRP7 function in pathogen defence and splicing abolishes binding. 相似文献
79.
Hannah M��ller David Schmidt Sandra Steinbrink Ekaterina Mirgorodskaya Verena Lehmann Karin Habermann Felix Dreher Niklas Gustavsson Thomas Kessler Hans Lehrach Ralf Herwig Johan Gobom Aspasia Ploubidou Michael Boutros Bodo M H Lange 《The EMBO journal》2010,29(19):3344-3357
Regulation of centrosome structure, duplication and segregation is integrated into cellular pathways that control cell cycle progression and growth. As part of these pathways, numerous proteins with well‐established non‐centrosomal localization and function associate with the centrosome to fulfill regulatory functions. In turn, classical centrosomal components take up functional and structural roles as part of other cellular organelles and compartments. Thus, although a comprehensive inventory of centrosome components is missing, emerging evidence indicates that its molecular composition reflects the complexity of its functions. We analysed the Drosophila embryonic centrosomal proteome using immunoisolation in combination with mass spectrometry. The 251 identified components were functionally characterized by RNA interference. Among those, a core group of 11 proteins was critical for centrosome structure maintenance. Depletion of any of these proteins in Drosophila SL2 cells resulted in centrosome disintegration, revealing a molecular dependency of centrosome structure on components of the protein translation machinery, actin‐ and RNA‐binding proteins. In total, we assigned novel centrosome‐related functions to 24 proteins and confirmed 13 of these in human cells. 相似文献
80.
Julian Weghuber Anna M. Lipp Jacqueline Stadlbauer Michael C. Aichinger Verena Ruprecht Alois Sonnleitner Gerhard J. Schütz Tamás Henics 《Cell biology international》2010,34(11):1109-1112
The cationic antimicrobial immunomodulatory peptide, KLK (KLKL5KLK), exerts profound membrane interacting properties, impacting on ultrastructure and fluidity. KLK–membrane interactions that lead to these alterations require the ability of the peptide to move into an α‐helical conformation. We show that KLK induces an increase of the intracellular Ca2+ concentration in human T24 cells. The effect of KLK is buffer‐sensitive, as it is detected when HBSS buffer is used, but not with PBS. This, together with the lack of effect of the middle leucine‐to‐proline‐substituted peptide derivative [KPK (KLKLLPLLKLK)], indicates that it is the conformational propensity rather than the net positive charge that contributes to the effect of KLK on intracellular Ca2+ level of T24 cells. We show that, although KLK slightly stimulates Ca2+ influx into the cell, the bulk increase of Ca2+ levels is due to KLK‐induced depletion of intracellular Ca2+ stores. Finally, we demonstrate a KLK‐induced switch of PS (phosphatidylserine) from the inner to the outer plasma membrane leaflet that contributes to the onset of early apoptotic changes in these cells. 相似文献