全文获取类型
收费全文 | 1086篇 |
免费 | 111篇 |
专业分类
1197篇 |
出版年
2024年 | 1篇 |
2023年 | 12篇 |
2022年 | 19篇 |
2021年 | 41篇 |
2020年 | 33篇 |
2019年 | 31篇 |
2018年 | 38篇 |
2017年 | 40篇 |
2016年 | 49篇 |
2015年 | 88篇 |
2014年 | 87篇 |
2013年 | 113篇 |
2012年 | 121篇 |
2011年 | 102篇 |
2010年 | 54篇 |
2009年 | 51篇 |
2008年 | 60篇 |
2007年 | 45篇 |
2006年 | 40篇 |
2005年 | 36篇 |
2004年 | 35篇 |
2003年 | 20篇 |
2002年 | 15篇 |
2001年 | 6篇 |
2000年 | 5篇 |
1999年 | 8篇 |
1998年 | 4篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 8篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 4篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1972年 | 1篇 |
1965年 | 1篇 |
1936年 | 1篇 |
排序方式: 共有1197条查询结果,搜索用时 15 毫秒
101.
102.
Hua Wong Hervé Marie-Nelly Sébastien Herbert Pascal Carrivain Hervé Blanc Romain Koszul Emmanuelle Fabre Christophe Zimmer 《Current biology : CB》2012,22(20):1881-1890
Highlights? We describe a predictive computational model of dynamic chromosomes in the yeast nucleus ? The model quantitatively recapitulates experimental data on nuclear organization ? The model predicts nuclear reorganization in response to treatment by rapamycin ? Large-scale nuclear organization is dominated by unspecific effects of crowded polymers 相似文献
103.
Froquet R le Coadic M Perrin J Cherix N Cornillon S Cosson P 《Molecular biology of the cell》2012,23(4):679-686
TM9 proteins form a family of conserved proteins with nine transmembrane domains essential for cellular adhesion in many biological systems, but their exact role in this process remains unknown. In this study, we found that genetic inactivation of the TM9 protein Phg1A dramatically decreases the surface levels of the SibA adhesion molecule in Dictyostelium amoebae. This is due to a decrease in sibA mRNA levels, in SibA protein stability, and in SibA targeting to the cell surface. A similar phenotype was observed in cells devoid of SadA, a protein that does not belong to the TM9 family but also exhibits nine transmembrane domains and is essential for cellular adhesion. A contact site A (csA)-SibA chimeric protein comprising only the transmembrane and cytosolic domains of SibA and the extracellular domain of the Dictyostelium surface protein csA also showed reduced stability and relocalization to endocytic compartments in phg1A knockout cells. These results indicate that TM9 proteins participate in cell adhesion by controlling the levels of adhesion proteins present at the cell surface. 相似文献
104.
R Pardoux S Sauge-Merle D Lemaire P Delangle L Guilloreau JM Adriano C Berthomieu 《PloS one》2012,7(8):e41922
To improve our understanding of uranium toxicity, the determinants of uranyl affinity in proteins must be better characterized. In this work, we analyzed the contribution of a phosphoryl group on uranium binding affinity in a protein binding site, using the site 1 EF-hand motif of calmodulin. The recombinant domain 1 of calmodulin from A. thaliana was engineered to impair metal binding at site 2 and was used as a structured template. Threonine at position 9 of the loop was phosphorylated in vitro, using the recombinant catalytic subunit of protein kinase CK2. Hence, the T9TKE12 sequence was substituted by the CK2 recognition sequence TAAE. A tyrosine was introduced at position 7, so that uranyl and calcium binding affinities could be determined by following tyrosine fluorescence. Phosphorylation was characterized by ESI-MS spectrometry, and the phosphorylated peptide was purified to homogeneity using ion-exchange chromatography. The binding constants for uranyl were determined by competition experiments with iminodiacetate. At pH 6, phosphorylation increased the affinity for uranyl by a factor of ∼5, from Kd = 25±6 nM to Kd = 5±1 nM. The phosphorylated peptide exhibited a much larger affinity at pH 7, with a dissociation constant in the subnanomolar range (Kd = 0.25±0.06 nM). FTIR analyses showed that the phosphothreonine side chain is partly protonated at pH 6, while it is fully deprotonated at pH 7. Moreover, formation of the uranyl-peptide complex at pH 7 resulted in significant frequency shifts of the νas(P-O) and νs(P-O) IR modes of phosphothreonine, supporting its direct interaction with uranyl. Accordingly, a bathochromic shift in νas(UO2)2+ vibration (from 923 cm−1 to 908 cm−1) was observed upon uranyl coordination to the phosphorylated peptide. Together, our data demonstrate that the phosphoryl group plays a determining role in uranyl binding affinity to proteins at physiological pH. 相似文献
105.
Marie-Line Maublanc Eric Bideau Romain Willemet Clara Bardonnet Georges Gonzalez Lionel Desneux Nicolas Cèbe Jean-François Gerard 《Comptes rendus biologies》2012,335(12):735-743
We studied the ranging behaviour and spatial relationships between seven roe deer during more than 4 years in a partly wooded 14.2-ha enclosure. The animals (three young males, four adult females) were monitored with GPS telemetry collars. As expected, the surface area and overlap of the males’ bimonthly ranges decreased, and the distance between their arithmetic centres increased, as they became adult and, for two of them, territorial. Unexpectedly, females also tended to space out, the surface area and overlap of their bimonthly ranges being minimal in May to June, i.e. during the birth period. The distance between their arithmetic centres reached its maximum at the same time. Overlap between females’ ranges was consistently lower than those between males and females’ ranges, or between 1-year old males’ ranges. Our results raise the questions of female seasonal territoriality and of independence of the spacing systems of the two sexes in roe deer. 相似文献
106.
107.
Vincent T Saikali P Cayrol R Roth AD Bar-Or A Prat A Antel JP 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(8):5730-5737
Autoantibody neuromyelitis optica-IgG (NMO-IgG) recognizing aquaporin-4 (AQP4) is implicated as playing a central role in the physiopathology of NMO. The aim of this in vitro-based study was to characterize functional consequences of interaction between NMO-IgG and cells of the neurovascular unit (astrocytes and brain endothelium) that would provide insight into recognized features of NMO, namely altered blood-brain barrier (BBB) permeability and granulocyte recruitment. We used sera from NMO and longitudinally extensive transverse myelitis cases shown to bind in a characteristic perivascular pattern to primate cerebellar slices. Using flow cytometry, we found that sera from NMO-IgG-positive patients reacted with CNS-derived human fetal astrocytes, whereas sera from multiple sclerosis patients did not. We demonstrated that NMO-IgG binding to astrocytes alters aquaporin-4 polarized expression and increases permeability of a human BBB endothelium/astrocyte barrier. We further demonstrated that NMO-IgG binding to human fetal astrocytes can result in NK cell degranulation, astrocyte killing by Ab-dependent cellular cytotoxicity and complement-dependent granulocyte attraction through the BBB model. Our study highlights important functional roles for NMO-IgG that could account for pathological lesions and BBB dysfunction observed in NMO. 相似文献
108.
Guilbaud M Chadeuf G Avolio F François A Moullier P Recchia A Salvetti A 《Journal of virology》2008,82(5):2590-2593
The p5 promoter region of the adeno-associated virus type 2 (AAV-2) rep gene has been described as essential for Rep-mediated site-specific integration (RMSSI) of plasmid sequences in human chromosome 19. We report here that insertion of a full-length or minimal p5 element between the viral inverted terminal repeats does not significantly increase RMSSI of a recombinant AAV (rAAV) vector after infection of growth-arrested or proliferating human cells. This result suggests that the p5 element may not improve RMSSI of rAAV vectors in vivo. 相似文献
109.
Hanana M Deluc L Fouquet R Daldoul S Léon C Barrieu F Ghorbel A Mliki A Hamdi S 《Comptes rendus biologies》2008,331(8):569-578
To identify and isolate genes related to abiotic stresses (salinity and drought) tolerance in grapevine, a candidate gene approach was developed and allowed isolating a full-length cDNA of rd22 gene from the Cabernet Sauvignon variety. The latter, named Vvrd22, is a dehydration-responsive gene that is usually induced by the application of exogenous ABA. Details of the physicochemical parameters and structural properties (molecular mass, secondary structure, conserved domains and motives, putative post-translational modification sites...) of the encoded protein have also been elucidated. The expression study of Vvrd22 was carried out at the berry growth stages and at the level of plant organs and tissues as well as under both drought and salt stresses. The results showed that Vvrd22 is constitutively expressed at a low level in all analyzed tissues. Moreover, salt stress induced Vvrd22 expression, particularly for the tolerant variety (Razegui), contrary to the sensitive one (Syrah), which did not display any expression variation during the stress, which means that Vvrd22 is involved in salt stress response and that its expression level depends on regulatory mechanisms that are efficient only for the tolerant variety. On the other hand, under drought stress, Vvrd22 is induced in an identical manner for both tolerant and sensitive varieties. In addition, stress signal molecules such as ABA (lonely applied or in combination with sucrose) induced Vvrd22 expression, even at a low level. A minimal knowledge about the role and the functionality of this gene is necessary and constitutes a prerequisite condition before starting and including Vvrd22 in any program of improvement of grapevine's abiotic stress tolerance. 相似文献
110.