全文获取类型
收费全文 | 420篇 |
免费 | 17篇 |
出版年
2024年 | 3篇 |
2023年 | 6篇 |
2022年 | 12篇 |
2021年 | 15篇 |
2020年 | 8篇 |
2019年 | 6篇 |
2018年 | 10篇 |
2017年 | 12篇 |
2016年 | 19篇 |
2015年 | 20篇 |
2014年 | 20篇 |
2013年 | 32篇 |
2012年 | 43篇 |
2011年 | 39篇 |
2010年 | 19篇 |
2009年 | 21篇 |
2008年 | 35篇 |
2007年 | 21篇 |
2006年 | 24篇 |
2005年 | 22篇 |
2004年 | 11篇 |
2003年 | 15篇 |
2002年 | 7篇 |
2001年 | 5篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1988年 | 2篇 |
1971年 | 1篇 |
1954年 | 1篇 |
排序方式: 共有437条查询结果,搜索用时 437 毫秒
81.
Sailendra?Singh Pallavi?Pandey Sumit?Ghosh Suchitra?BanerjeeEmail author 《Protoplasma》2018,255(5):1387-1400
Andrographolide (AD) is the time-honoured pharmacologically active constituent of the traditionally renowned medicinal plant—Andrographis paniculata. Advancements in the target-oriented drug discovery process have further unravelled the immense therapeutic credibility of another unique molecule—neoandrographolide (NAD). The escalated market demand of these anti-cancer diterpenes is increasingly facing unrelenting hurdles of demand and supply disparity, attributable to their limited yield. Callus and adventitious root cultures were generated to explore their biosynthetic potentials which first time revealed NAD production along with AD. Optimization of the types and concentrations of auxins along with media form and cultivation time led to the successful tuning towards establishing adventitious roots as a superior production alternative for both AD/NAD. Supplementation of IBA to the NAA + Kn-containing MS medium boosted the overall growth and AD/NAD synthesis in the adventitious roots. Compared to control leaves, the adventitious root exhibited about 2.61- and 8.8-fold higher contents of AD and NAD, respectively. The qRT-PCR involving nine key pathway genes was studied, which revealed upregulation of GGPS1 and HMGR1/2 genes and downregulation of DXS1/2 and HDR1/2 genes in the adventitious root as compared to that in the control leaves. Such observations highlight that in vitro cultures can serve as efficient production alternatives for AD/NAD as the cytosolic genes (HMGR1/2 of MVA pathway) are competent enough to take over from the plastidial genes (DXS1/2 and HDR1/2 of MEP pathway), provided the accredited first branch-point regulatory gene (GGPS) expression and the culture requirements are optimally fulfilled. 相似文献
82.
Simulation Based Investigation of Deleterious nsSNPs in ATXN2 Gene and Its Structural Consequence Toward Spinocerebellar Ataxia
下载免费PDF全文
![点击此处可从《Journal of cellular biochemistry》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Siddharth Sinha Sharad Verma Aditi Singh Pallavi Somvanshi Abhinav Grover 《Journal of cellular biochemistry》2018,119(1):499-510
Spinocerebellar degeneration, termed as ataxia is a neurological disorder of central nervous system, characterized by limb in‐coordination and a progressive gait. The patient also demonstrates specific symptoms of muscle weakness, slurring of speech, and decreased vibration senses. Expansion of polyglutamine trinucleotide (CAG) within ATXN2 gene with 35 or more repeats, results in spinocerebellar ataxia type‐2. Protein ataxin‐2 coded by ATXN2 gene has been reported to have a crucial role in translation of the genetic information through sequestering the histone acetyl transferases (HAT) resulting in a state of hypo‐acetylation. In the present study, we have evaluated the outcome for 122 non synonymous single nucleotide polymorphisms (nsSNPs) reported within ATXN2 gene through computational tools such as SIFT, PolyPhen 2.0, PANTHER, I‐mutant 2.0, Phd‐SNP, Pmut, MutPred. The apo and mutant (L305V and Q339L) form of structures for the ataxin‐2 protein were modeled for gaining insights toward 3D spatial arrangement. Further, molecular dynamics simulations and structural analysis were performed to observe the brunt of disease associated nsSNPs toward the strength and secondary properties of ataxin‐2 protein structure. Our results showed that, L305V is a highly deleterious and disease causing point substitution. Analysis based on RMSD, RMSF, Rg, SASA, number of hydrogen bonds (NH bonds), covariance matrix trace, projection analysis for eigen vector demonstrated a significant instability and conformation along with rise in mutant flexibility values in comparison to the apo form of ataxin‐2 protein. The study provides a blue print of computational methodologies to examine the ataxin‐blend SNPs. J. Cell. Biochem. 119: 499–510, 2018. © 2017 Wiley Periodicals, Inc. 相似文献
83.
Aspartate‐β‐semialdeyhyde dehydrogenase as a potential therapeutic target of Mycobacterium tuberculosis H37Rv: Evidence from in silico elementary mode analysis of biological network model
下载免费PDF全文
![点击此处可从《Journal of cellular biochemistry》网站下载免费的PDF全文](/ch/ext_images/free.gif)
84.
Geetha Thiagarajan Andrew Semple Jose K. James Jason K. Cheung Mohammed Shameem 《MABS-AUSTIN》2016,8(6):1088-1097
With the rapid growth of biopharmaceutical product development, knowledge of therapeutic protein stability has become increasingly important. We evaluated assays that measure solution-mediated interactions and key molecular characteristics of 9 formulated monoclonal antibody (mAb) therapeutics, to predict their stability behavior. Colloidal interactions, self-association propensity and conformational stability were measured using effective surface charge via zeta potential, diffusion interaction parameter (kD) and differential scanning calorimetry (DSC), respectively. The molecular features of all 9 mAbs were compared to their stability at accelerated (25°C and 40°C) and long-term storage conditions (2–8°C) as measured by size exclusion chromatography. At accelerated storage conditions, the majority of the mAbs in this study degraded via fragmentation rather than aggregation. Our results show that colloidal stability, self-association propensity and conformational characteristics (exposed tryptophan) provide reasonable prediction of accelerated stability, with limited predictive value at 2–8°C stability. While no correlations to stability behavior were observed with onset-of-melting temperatures or domain unfolding temperatures, by DSC, melting of the Fab domain with the CH2 domain suggests lower stability at stressed conditions. The relevance of identifying appropriate biophysical assays based on the primary degradation pathways is discussed. 相似文献
85.
86.
DG Crider LJ García-Rodríguez P Srivastava L Peraza-Reyes K Upadhyaya IR Boldogh LA Pon 《The Journal of cell biology》2012,198(5):793-798
The Chk2-mediated deoxyribonucleic acid (DNA) damage checkpoint pathway is important for mitochondrial DNA (mtDNA) maintenance. We show in this paper that mtDNA itself affects cell cycle progression. Saccharomyces cerevisiae rho(0) cells, which lack mtDNA, were defective in G1- to S-phase progression. Deletion of subunit Va of cytochrome c oxidase, inhibition of F(1)F(0) adenosine triphosphatase, or replacement of all mtDNA-encoded genes with noncoding DNA did not affect G1- to S-phase progression. Thus, the cell cycle progression defect in rho(0) cells is caused by loss of DNA within mitochondria and not loss of respiratory activity or mtDNA-encoded genes. Rad53p, the yeast Chk2 homologue, was required for inhibition of G1- to S-phase progression in rho(0) cells. Pif1p, a DNA helicase and Rad53p target, underwent Rad53p-dependent phosphorylation in rho(0) cells. Thus, loss of mtDNA activated an established checkpoint kinase that inhibited G1- to S-phase progression. These findings support the existence of a Rad53p-regulated checkpoint that regulates G1- to S-phase progression in response to loss of mtDNA. 相似文献
87.
Pallavi Singh A. Cody Springman H. Dele Davies Shannon D. Manning 《Journal of bacteriology》2012,194(21):6005
This report highlights the whole-genome shotgun draft sequence for a Streptococcus agalactiae strain representing multilocus sequence type (ST) 17, isolated from a colonized woman at 8 weeks postpartum. This sequence represents an important addition to the published genomes and will promote comparative genomic studies of S. agalactiae recovered from diverse sources. 相似文献
88.
Sahil Mahfooz Pallavi Singh Deepak K Maurya Mahesh C Yadav Azram Tahoor Harmesh Sahay Arpita Srivastava Anil Prakash 《Bioinformation》2012,8(23):1171-1175
The frequency and distribution of microsatellites were analyzed in the 19 mitogenomes of phytopathogenic fungi covering five
phyla. Our analysis revealed that in all the mitogenomes studied, the frequency and relative abundance varied, and it was neither
influenced by genome size nor by GC content. SSRs were found to be differential distributed in genic and intergenic regions. An
average of 5.14 (23.6%) SSRs were present in genic sequences and 21.7 (76.4%) SSRs were located in the intergenic sequences.
Relative abundance of SSRs in mitogenomes was the highest in Aspergillus tubigensis, whereas, it was the least in Phaeosphaeria
nodurum, the average being 0.45. Trinucleotide repeats were the most abundant motifs in the genic and intergenic regions of the
mitogenomes of the phytopathogenic fungi. Among the genes, cox1 harbors the maximum SSRs, whereas cox3 and nad 7 contain the
least. Based on the presence of SSRs in a particular gene, genetic relationships among individual organisms were also established. 相似文献
89.
Singh MK Gupta G Boopathi M Gupta P Chauhan V Tomar A Singh L Dhaked RK 《Protein and peptide letters》2012,19(5):530-537
The most effective protection against toxin is inducing protective immune response through vaccination that will produce neutralizing antibodies. Antibodies will bind to and clear toxin from the circulation before it can enter nerve cells and block neurotransmission and can also be used for development of detection system. In the present study we constructed a deletion mutant of the binding domain (1098-1296) to produce smallest toxin fragment as vaccine candidate against BoNT/A. The BoNT/A-HCC protein was highly expressed in Escherichia coli SG13009 and found to form inclusion bodies. The purified inclusion bodies were solubilized in 6 M guanidine-HCl containing 10 mM β-mercaptoethanol and 20 mM imidazole and the rBoNT/A-HCC was purified and refolded in a single step on Ni2+ affinity column. The purified protein was ~98 % pure as assessed by SDS-polyacrylamide gel with the yield of 8 mg/L and showed binding to polysialoganglioside (GT1b). The rBoNT/A-HCC at dose of 40 μg/mouse generated high IgG antibody titre with predominance of IgG1 subtype, but failed to protect animals against BoNT/A challenge. Antibody titre in serum was determined by enzyme linked immunosorbent assay and specific binding to rBoNT/A-HCC was demonstrated by surface plasmon resonance (SPR), with a dissociation constant of 0.8 pM. 相似文献
90.
About 10% of the coding capacity of the Mycobacterium tuberculosis (M. tb) genome is devoted to the PE/PPE family of genes scattered throughout the genome. We have identified 28 PE/PPE operons which are organized within the M. tb genome in such a way that most PE members are upstream to PPE members. One example of such a gene arrangement is the PPE gene Rv2430c, earlier shown by us to code for a highly antigenic protein eliciting strong B-cell responses in TB patients [Choudhary, R.K., Mukhopadhyay, S., Chakhaiyar, P., Sharma, N., Murthy, K.J.R., Katoch V.M. and Hasnain, S.E. (2003) PPE antigen Rv2430c of Mycobacterium tuberculosis induces a strong B cell response. Infect. Immun. 71, 6338-6343], situated downstream to PE gene Rv2431c. Rv2431c and Rv2430c are transcribed as an operon. Expression of either rRv2431c or rRv2430c alone in E. coli limited their localization to the inclusion bodies. However, when they were co-expressed, both the proteins appeared in the soluble fraction. These two proteins interact with each other and form oligomers when alone, however, when present together they exist as heteromer. 相似文献