全文获取类型
收费全文 | 548篇 |
免费 | 55篇 |
国内免费 | 1篇 |
出版年
2024年 | 1篇 |
2023年 | 4篇 |
2022年 | 2篇 |
2021年 | 22篇 |
2020年 | 7篇 |
2019年 | 20篇 |
2018年 | 17篇 |
2017年 | 15篇 |
2016年 | 22篇 |
2015年 | 48篇 |
2014年 | 47篇 |
2013年 | 51篇 |
2012年 | 54篇 |
2011年 | 29篇 |
2010年 | 27篇 |
2009年 | 31篇 |
2008年 | 31篇 |
2007年 | 29篇 |
2006年 | 33篇 |
2005年 | 25篇 |
2004年 | 19篇 |
2003年 | 15篇 |
2002年 | 10篇 |
2001年 | 4篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 4篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1992年 | 1篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1983年 | 1篇 |
1960年 | 1篇 |
1957年 | 1篇 |
1956年 | 1篇 |
1955年 | 1篇 |
1947年 | 2篇 |
1946年 | 1篇 |
1937年 | 2篇 |
1934年 | 4篇 |
1933年 | 1篇 |
1931年 | 1篇 |
1929年 | 2篇 |
1928年 | 2篇 |
1926年 | 1篇 |
1925年 | 1篇 |
排序方式: 共有604条查询结果,搜索用时 73 毫秒
51.
Caspar Elo Christensen Magnus Karlsson Jakob R. Winther Pernille Rose Jensen Mathilde H. Lerche 《The Journal of biological chemistry》2014,289(4):2344-2352
Accumulating evidence suggest that the pyridine nucleotide NAD has far wider biological functions than its classical role in energy metabolism. NAD is used by hundreds of enzymes that catalyze substrate oxidation and, as such, it plays a key role in various biological processes such as aging, cell death, and oxidative stress. It has been suggested that changes in the ratio of free cytosolic [NAD+]/[NADH] reflects metabolic alterations leading to, or correlating with, pathological states. We have designed an isotopically labeled metabolic bioprobe of free cytosolic [NAD+]/[NADH] by combining a magnetic enhancement technique (hyperpolarization) with cellular glycolytic activity. The bioprobe reports free cytosolic [NAD+]/[NADH] ratios based on dynamically measured in-cell [pyruvate]/[lactate] ratios. We demonstrate its utility in breast and prostate cancer cells. The free cytosolic [NAD+]/[NADH] ratio determined in prostate cancer cells was 4 times higher than in breast cancer cells. This higher ratio reflects a distinct metabolic phenotype of prostate cancer cells consistent with previously reported alterations in the energy metabolism of these cells. As a reporter on free cytosolic [NAD+]/[NADH] ratio, the bioprobe will enable better understanding of the origin of diverse pathological states of the cell as well as monitor cellular consequences of diseases and/or treatments. 相似文献
52.
Prospective Studies Exploring the Possible Impact of an ID3 Polymorphism on Changes in Obesity Measures 下载免费PDF全文
53.
Janejira Duangjit Mathilde Causse Christopher Sauvage 《Molecular breeding : new strategies in plant improvement》2016,36(3):29
Fruit quality is polygenic; each component has variable heritability and is difficult to assess. Genomic selection, which allows the prediction of phenotypes based on the whole-genome genotype, could vastly help to improve fruit quality. The goal of this study is to evaluate the accuracy of genomic selection for several metabolomic and quality traits by cross-validation and to estimate the impact of different factors on its accuracy. We analyzed data from 45 phenotypic traits and genotypic data obtained from a previous study of genetic association on a collection of 163 tomato accessions. We tested the influence of (1) the size of training population, (2) the number and density of molecular markers and (3) individual relatedness on the accuracy of prediction. The prediction accuracy of phenotypic values was largely related to the heritability of the traits. The size of training population increased the accuracy of predictions. Using 122 accessions and 5995 single nucleotide polymorphisms (SNPs) was the optimal condition. The density of markers and their numbers also affected the accuracy of the prediction. Using 2313 SNP markers distributed 0.1 cM or more apart from each other reduced the accuracy of prediction, and no gain in prediction accuracy was found when more markers were used in the model. Additionally, the more accessions were related, the more accurate were the predictions. Finally, the structure of the population negatively affected the prediction accuracy. In conclusion, the results obtained by cross-validation illustrated the effect of several parameters on the accuracy of prediction and revealed the potential of genomic selection in tomato breeding programs. 相似文献
54.
Mathilde Doyard Daniel Chappard Patricia Leroyer Marie-Paule Roth Olivier Loréal Pascal Guggenbuhl 《PloS one》2016,11(2)
Osteoporosis may complicate iron overload diseases such as genetic hemochromatosis. However, molecular mechanisms involved in the iron-related osteoporosis remains poorly understood. Recent in vitro studies support a role of osteoblast impairment in iron-related osteoporosis. Our aim was to analyse the impact of excess iron in Hfe-/- mice on osteoblast activity and on bone microarchitecture. We studied the bone formation rate, a dynamic parameter reflecting osteoblast activity, and the bone phenotype of Hfe−/− male mice, a mouse model of human hemochromatosis, by using histomorphometry. Hfe−/− animals were sacrificed at 6 months and compared to controls. We found that bone contains excess iron associated with increased hepatic iron concentration in Hfe−/− mice. We have shown that animals with iron overload have decreased bone formation rate, suggesting a direct impact of iron excess on active osteoblasts number. For bone mass parameters, we showed that iron deposition was associated with bone loss by producing microarchitectural impairment with a decreased tendency in bone trabecular volume and trabecular number. A disorganization of trabecular network was found with marrow spaces increased, which was confirmed by enhanced trabecular separation and star volume of marrow spaces. These microarchitectural changes led to a loss of connectivity and complexity in the trabecular network, which was confirmed by decreased interconnectivity index and increased Minkowski’s fractal dimension. Our results suggest for the first time in a genetic hemochromatosis mouse model, that iron overload decreases bone formation and leads to alterations in bone mass and microarchitecture. These observations support a negative effect of iron on osteoblast recruitment and/or function, which may contribute to iron-related osteoporosis. 相似文献
55.
Boureau T Siamer S Perino C Gaubert S Patrit O Degrave A Fagard M Chevreau E Barny MA 《Molecular plant-microbe interactions : MPMI》2011,24(5):577-584
Erwinia amylovora is responsible for fire blight of apple and pear trees. Its pathogenicity depends on a type III secretion system (T3SS) mediating the translocation of effectors into the plant cell. The DspA/E effector suppresses callose deposition on apple leaves. We found that E. amylovora and Pseudomonas syringae DC3000 tts mutants or peptide flg22 do not trigger callose deposition as strongly as the dspA/E mutant on apple leaves. This suggests that, on apple leaves, callose deposition is poorly elicited by pathogen-associated molecular patterns (PAMPs) such as flg22 or other PAMPs harbored by tts mutants and is mainly elicited by injected effectors or by the T3SS itself. Callose elicitation partly depends on HrpW because an hrpW-dspA/E mutant elicits lower callose deposition than a dspA/E mutant. Furthermore, an hrpN-dspA/E mutant does not trigger callose deposition, indicating that HrpN is required to trigger this plant defense reaction. We showed that HrpN plays a general role in the translocation process. Thus, the HrpN requirement for callose deposition may be explained by its role in translocation: HrpN could be involved in the translocation of other effectors inducing callose deposition. Furthermore, HrpN may also directly contribute to the elicitation process because we showed that purified HrpN induces callose deposition. 相似文献
56.
57.
Peroxisomal Hydrogen Peroxide Is Coupled to Biotic Defense Responses by ISOCHORISMATE SYNTHASE1 in a Daylength-Related Manner 总被引:1,自引:0,他引:1
58.
59.
Paris M Escriva H Schubert M Brunet F Brtko J Ciesielski F Roecklin D Vivat-Hannah V Jamin EL Cravedi JP Scanlan TS Renaud JP Holland ND Laudet V 《Current biology : CB》2008,18(11):825-830
Most studies in evolution are centered on how homologous genes, structures, and/or processes appeared and diverged. Although historical homology is well defined as a concept, in practice its establishment can be problematic, especially for some morphological traits or developmental processes. Metamorphosis in chordates is such an enigmatic character. Defined as a spectacular postembryonic larva-to-adult transition, it shows a wide morphological diversity between the different chordate lineages, suggesting that it might have appeared several times independently. In vertebrates, metamorphosis is triggered by binding of the thyroid hormones (THs) T(4) and T(3) to thyroid-hormone receptors (TRs). Here we show that a TH derivative, triiodothyroacetic acid (TRIAC), induces metamorphosis in the cephalochordate amphioxus. The amphioxus TR (amphiTR) mediates spontaneous and TRIAC-induced metamorphosis because it strongly binds to TRIAC, and a specific TR antagonist, NH3, inhibits both spontaneous and TRIAC-induced metamorphosis. Moreover, as in amphibians, amphiTR expression levels increase around metamorphosis and are enhanced by THs. Therefore, TH-regulated metamorphosis, mediated by TR, is an ancestral feature of all chordates. This conservation of a regulatory network supports the homology of metamorphosis in the chordate lineage. 相似文献
60.
The initiation of meiotic recombination by the formation of DNA double-strand breaks (DSBs) catalysed by the Spo11 protein is strongly evolutionary conserved. In Saccharomyces cerevisiae, Spo11 requires nine other proteins for meiotic DSB formation, but, unlike Spo11, few of these proteins seem to be conserved across kingdoms. In order to investigate this recombination step in higher eukaryotes, we have isolated a new gene, AtPRD1, whose mutation affects meiosis in Arabidopsis thaliana. In Atprd1 mutants, meiotic recombination rates fall dramatically, early recombination markers (e.g., DMC1 foci) are absent, but meiosis progresses until achiasmatic univalents are formed. Besides, Atprd1 mutants suppress DSB repair defects of a large range of meiotic mutants, showing that AtPRD1 is involved in meiotic recombination and is required for meiotic DSB formation. Furthermore, we showed that AtPRD1 and AtSPO11-1 interact in a yeast two-hybrid assay, suggesting that AtPRD1 could be a partner of AtSPO11-1. Moreover, our study reveals similarity between AtPRD1 and the mammalian protein Mei1, suggesting that AtPRD1 could be a Mei1 functional homologue. 相似文献