全文获取类型
收费全文 | 1296篇 |
免费 | 85篇 |
国内免费 | 1篇 |
出版年
2023年 | 8篇 |
2022年 | 19篇 |
2021年 | 35篇 |
2020年 | 27篇 |
2019年 | 23篇 |
2018年 | 36篇 |
2017年 | 28篇 |
2016年 | 43篇 |
2015年 | 47篇 |
2014年 | 79篇 |
2013年 | 89篇 |
2012年 | 99篇 |
2011年 | 102篇 |
2010年 | 69篇 |
2009年 | 45篇 |
2008年 | 52篇 |
2007年 | 52篇 |
2006年 | 47篇 |
2005年 | 53篇 |
2004年 | 32篇 |
2003年 | 31篇 |
2002年 | 29篇 |
2001年 | 29篇 |
2000年 | 22篇 |
1999年 | 22篇 |
1998年 | 10篇 |
1997年 | 6篇 |
1996年 | 9篇 |
1994年 | 10篇 |
1992年 | 15篇 |
1991年 | 9篇 |
1990年 | 10篇 |
1989年 | 10篇 |
1988年 | 12篇 |
1987年 | 7篇 |
1986年 | 12篇 |
1985年 | 6篇 |
1984年 | 12篇 |
1983年 | 8篇 |
1982年 | 9篇 |
1980年 | 8篇 |
1979年 | 13篇 |
1978年 | 11篇 |
1977年 | 7篇 |
1976年 | 7篇 |
1975年 | 8篇 |
1974年 | 5篇 |
1973年 | 10篇 |
1972年 | 6篇 |
1969年 | 5篇 |
排序方式: 共有1382条查询结果,搜索用时 15 毫秒
151.
Bhattacharya M Mukhopadhyay C Chakrabarti A 《Journal of biomolecular structure & dynamics》2006,24(3):269-276
The hydrophobic fluorescent probe Prodan binds to the self-associating domain of spectrin with 1:1 stoichiometry. A model of the self-associating domain was generated based on its homology with other domains of spectrin. Prodan was then docked onto the model, and several sites with low interaction energy were identified. To verify whether the binding of Prodan is specific towards the self-associating domain of spectrin, it was docked on to several other domains of spectrin, having a known three-dimensional structure. Analysis of the docking results suggests that the binding of Prodan to the self-associating domain of spectrin will involve hydrophobic and hydrophilic groups of Prodan. The results clearly indicate the preference of Prodan for a particular binding site of the self-associating domain. 相似文献
152.
Sahoo R Dutta T Das A Sinha Ray S Sengupta R Ghosh S 《Free radical biology & medicine》2006,40(4):625-631
Oxidative stress has been shown to alter cellular redox status in various cell types. Changes in expressions of several antioxidative and antistress-responsive genes along with activation or inactivation of various proteins were also reported during oxidative insult as well as during nitrosative stress. In the present study, we show the effect of nitrosative stress on cellular redox status of fission yeast Schizosaccharomyces pombe. This is the first report of S-nitrosoglutathione (GSNO) reductase activity in S. pombe and its inactivation by GSNO. We also show the inactivation of glutathione reductase (GR) and glutathione peroxidase in the presence of various reactive nitrogen species in vivo. In addition, we first observe the inactivation of GR by peroxynitrite in vivo using S. pombe cells and also similar observations under in vitro conditions. An immunoreactive band against monoclonal anti-3-nitrotyrosine antibody confirms the modification of GR under in vitro conditions. We also show the effect of nitrosative stress on Deltapap1 cells of S. pombe, which are more sensitive to nitrosative stress, indicating the involvement of Pap1 in the protection against nitrosative stress. Finally, exposure of S. pombe cells to reactive nitrogen species reveals an important role of cellular thiol pool in protection against nitrosative stress. 相似文献
153.
Local similarity analysis reveals unique associations among marine bacterioplankton species and environmental factors 总被引:1,自引:0,他引:1
Ruan Q Dutta D Schwalbach MS Steele JA Fuhrman JA Sun F 《Bioinformatics (Oxford, England)》2006,22(20):2532-2538
MOTIVATION: Characterizing the diversity of microbial communities and understanding the environmental factors that influence community diversity are central tenets of microbial ecology. The development and application of cultivation independent molecular tools has allowed for rapid surveying of microbial community composition at unprecedented resolutions and frequencies. There is a growing need to discern robust patterns and relationships within these datasets which provide insight into microbial ecology. Pearson correlation coefficient (PCC) analysis is commonly used for identifying the linear relationship between two species, or species and environmental factors. However, this approach may not be able to capture more complex interactions which occur in situ; thus, alternative analyses were explored. RESULTS: In this paper we introduced local similarity analysis (LSA), which is a technique that can identify more complex dependence associations among species as well as associations between species and environmental factors without requiring significant data reduction. To illustrate its capability of identifying relationships that may not otherwise be identified by PCC, we first applied LSA to simulated data. We then applied LSA to a marine microbial observatory dataset and identified unique, significant associations that were not detected by PCC analysis. LSA results, combined with results from PCC analysis were used to construct a theoretical ecological network which allows for easy visualization of the most significant associations. Biological implications of the significant associations detected by LSA were discussed. We also identified additional applications where LSA would be beneficial. AVAILABILITY: The algorithms are implemented in Splus/R and they are available upon request from the corresponding author. 相似文献
154.
Tui Ray Indrajit Dutta Prasenjit Saha Sampa Das S.C. Roy 《Plant Cell, Tissue and Organ Culture》2006,85(1):11-21
An efficient micropropagation protocol produced large number of plants of the three elite banana (Musa spp.) cultivars Robusta (AAA), Giant Governor (AAA) and Martaman (AAB) from shoot tip meristem. The genetic relationships
and fidelity among the cultivars and micropropagated plants as assessed by random amplified polymorphic DNA (RAPD) and inter-simple
sequence repeat (ISSR) markers, revealed three somaclonal variants from Robusta and three from Giant Governor. A total of
5330 RAPD and 2741 ISSR fragments were generated with 21 RAPD and 12 ISSR primers in micropropagated plants. The percentage
of polymorphic loci by RAPD and ISSR were found to be 1.75, 5.08 in Robusta and 0.83, 5.0 in Giant Governor respectively.
Among the two marker systems used, ISSR fingerprinting detected more polymorphism than RAPD in Robusta and Giant Governor
with most of the primers showing similar fingerprinting profile, whereas Martaman revealed complete genetic stability. 相似文献
155.
Sengupta R Sahoo R Ray SS Dutta T Dasgupta A Ghosh S 《Molecular and cellular biochemistry》2006,284(1-2):117-126
The oxygenase domain of the inducible nitric oxide synthase, Δ65 iNOSox is a dimer that binds heme, L-Arginine (L-Arg), and tetrahydrobiopterin (H4B) and is the site for NO synthesis. The role of H4B in iNOS structure-function is complex and its exact structural role is presently unknown. The present paper provides a simple
mechanistic account of interaction of the cofactor tetrahydrobiopterin (H4B) with the bacterially expressed Δ65 iNOSox protein. Transverse urea gradient gel electrophoresis studies indicated the presence
of different conformers in the cofactor-incubated and cofactor-free Δ65 iNOSox protein. Dynamic Light Scattering (DLS) studies
of cofactor-incubated and cofactor-free Δ65 iNOSox protein also showed two distinct populations of two different diameter
ranges. Cofactor tetrahydrobiopterin (H4B) shifted one population, with higher diameter, to the lower diameter ranges indicating conformational changes. The additional
role played by the cofactor is to elevate the heme retaining capacity even in presence of denaturing stress. Together, these
findings confirm that the H4B is essential in modulating the iNOS heme environment and the protein environment in the dimeric iNOS oxygenase domain. (Mol
Cell Boichem xxx: 1–10, 2005)
Supported by Calcutta University Research Grants. 相似文献
156.
Effect of controlled carbon dioxide on in vitro shoot multiplication in Feronia limonia (L.) Swingle
The effect of controlled carbon dioxide environment on in vitro shoot growth and multiplication in Feronia limonia (a tropical fruit plant, Family- Rutaceae) was studied. Carbon dioxide available in the ambient air of the growth room was
insufficient for in vitro growth of the shoots alone. Also, the presence of sucrose only as the C-source in the medium (without CO2), was found to be inadequate for sustainable growth and multiplication of shoots. The carbon dioxide enrichment promoted
shoot multiplication and overall growth. The promotory effect of CO2 was independent of the presence of sucrose in the medium. In the presence of both CO2 and sucrose, an additive effect was observed producing maximum shoot growth. In the absence of sucrose a higher concentration
of CO2 (10.0)g m−3 was required to achieve photoautotrophic shoot multiplication comparable to ambient air controls. Highest leaf area per shoot
cluster promoting shoot growth and multiplication was recorded under this treatment. Shoots growing on sucrose containing
medium under controlled CO2 environment of 0.6 g m−3 concentration evoked better response than ambient air controls (shoots growing on sucrose containing medium) in growth room.
This treatment produced the overall best response. The present study highlighted the possibility of photoautotrophic multiplication
which might prove useful for successful hardening and acclimatization in tissue culture plants. 相似文献
157.
A deletion at the mouse Xist gene exposes trans-effects that alter the heterochromatin of the inactive X chromosome and the replication time and DNA stability of both X chromosomes 下载免费PDF全文
Diaz-Perez SV Ferguson DO Wang C Csankovszki G Wang C Tsai SC Dutta D Perez V Kim S Eller CD Salstrom J Ouyang Y Teitell MA Kaltenboeck B Chess A Huang S Marahrens Y 《Genetics》2006,174(3):1115-1133
The inactive X chromosome of female mammals displays several properties of heterochromatin including late replication, histone H4 hypoacetylation, histone H3 hypomethylation at lysine-4, and methylated CpG islands. We show that cre-Lox-mediated excision of 21 kb from both Xist alleles in female mouse fibroblasts led to the appearance of two histone modifications throughout the inactive X chromosome usually associated with euchromatin: histone H4 acetylation and histone H3 lysine-4 methylation. Despite these euchromatic properties, the inactive X chromosome was replicated even later in S phase than in wild-type female cells. Homozygosity for the deletion also caused regions of the active X chromosome that are associated with very high concentrations of LINE-1 elements to be replicated very late in S phase. Extreme late replication is a property of fragile sites and the 21-kb deletions destabilized the DNA of both X chromosomes, leading to deletions and translocations. This was accompanied by the phosphorylation of p53 at serine-15, an event that occurs in response to DNA damage, and the accumulation of gamma-H2AX, a histone involved in DNA repair, on the X chromosome. The Xist locus therefore maintains the DNA stability of both X chromosomes. 相似文献
158.
Targeted comparative RNA interference analysis reveals differential requirement of genes essential for cell proliferation 下载免费PDF全文
Machida YJ Chen Y Machida Y Malhotra A Sarkar S Dutta A 《Molecular biology of the cell》2006,17(11):4837-4845
Differences in the genetic and epigenetic make up of cell lines have been very useful for dissecting the roles of specific genes in the biology of a cell. Targeted comparative RNAi (TARCOR) analysis uses high throughput RNA interference (RNAi) against a targeted gene set and rigorous quantitation of the phenotype to identify genes with a differential requirement for proliferation between cell lines of different genetic backgrounds. To demonstrate the utility of such an analysis, we examined 257 growth-regulated genes in parallel in a breast epithelial cell line, MCF10A, and a prostate cancer cell line, PC3. Depletion of an unexpectedly high number of genes (25%) differentially affected proliferation of the two cell lines. Knockdown of many genes that spare PC3 (p53-) but inhibit MCF10A (p53+) proliferation induces p53 in MCF10A cells. EBNA1BP2, involved in ribosome biogenesis, is an example of such a gene, with its depletion arresting MCF10A at G1/S in a p53-dependent manner. TARCOR is thus useful for identifying cell type-specific genes and pathways involved in proliferation and also for exploring the heterogeneity of cell lines. In particular, our data emphasize the importance of considering the genetic status, when performing siRNA screens in mammalian cells. 相似文献
159.
Chakraborty J Ghosal D Dutta A Dutta TK 《Journal of biomolecular structure & dynamics》2012,30(4):419-436
Bacterial aromatic ring-hydroxylating oxygenases (RHOs) are multicomponent enzyme systems which have potential utility in bioremediation of aromatic compounds in the environment. To cope with the enormous diversity of aromatic compounds in the environment, this enzyme family has evolved remarkably exhibiting broad substrate specificity. RHOs are multicomponent enzymes comprising of a homo- or hetero-multimeric terminal oxygenase and one or more electron transport (ET) protein(s). The present study attempts in depicting the evolutionary scenarios that might have occurred during the evolution of RHOs, by analyzing a set of available sequences including those obtained from complete genomes. A modified classification scheme identifying four new RHO types has been suggested on the basis of their evolutionary and functional behaviours, in relation to structural configuration of substrates and preferred oxygenation site(s). The present scheme emphasizes on the fact that the phylogenetic affiliation of RHOs is distributed among four distinct 'Similarity classes', independent of the constituent ET components. Similar combination of RHO components that was previously considered to be equivalent and classified together [Kweon et al., BMC Biochemistry 9, 11 (2008)] were found here in distinct similarity classes indicating the role of substrate-binding terminal oxygenase in guiding the evolution of RHOs irrespective of the nature of constituent ET components. Finally, a model for evolution of the multicomponent RHO enzyme system has been proposed, beginning from genesis of the terminal oxygenase components followed by recruitment of constituent ET components, finally evolving into various 'extant' RHO types. 相似文献
160.
The phosphoesterase (PE) domain of the bacterial DNA repair enzyme LigD possesses distinctive manganese-dependent 3′-phosphomonoesterase and 3′-phosphodiesterase activities. PE exemplifies a new family of DNA end-healing enzymes found in all phylogenetic domains. Here, we determined the structure of the PE domain of Pseudomonas aeruginosa LigD (PaePE) using solution NMR methodology. PaePE has a disordered N-terminus and a well-folded core that differs in instructive ways from the crystal structure of a PaePE•Mn2+• sulfate complex, especially at the active site that is found to be conformationally dynamic. Chemical shift perturbations in the presence of primer-template duplexes with 3′-deoxynucleotide, 3′-deoxynucleotide 3′-phosphate, or 3′ ribonucleotide termini reveal the surface used by PaePE to bind substrate DNA and suggest a more efficient engagement in the presence of a 3′-ribonucleotide. Spectral perturbations measured in the presence of weakly catalytic (Cd2+) and inhibitory (Zn2+) metals provide evidence for significant conformational changes at and near the active site, compared to the relatively modest changes elicited by Mn2+. 相似文献