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31.
Richard K. Amewu James Chadwick Afthab Hussain Somnath Panda Rinki Rinki Omar Janneh Stephen A. Ward Candel Miguel Hollie Burrell-Saward Livia Vivas Paul M. O’Neill 《Bioorganic & medicinal chemistry》2013,21(23):7392-7397
The synthesis of a range of mono spiro and dispiro 1,2,4,5-tetraoxane dimers is described. Selected molecules were examined in in vitro assays to determine their antimalarial and anticancer potential. Our studies reveal that several molecules possess potent nanomolar antimalarial and single digit micromolar antiproliferative IC50s versus colon (HT29-AK and leukemia (HL60) cell lines. 相似文献
32.
Tapan Kumar Mohanta Nibedita Mohanta Pratap Parida Sujogya Kumar Panda Lakshmi Narayanan Ponpandian Hanhong Bae 《PloS one》2016,11(2)
The mitogen-activated protein kinase (MAPK) is characterized by the presence of the T-E-Y, T-D-Y, and T-G-Y motifs in its activation loop region and plays a significant role in regulating diverse cellular responses in eukaryotic organisms. Availability of large-scale genome data in the fungal kingdom encouraged us to identify and analyse the fungal MAPK gene family consisting of 173 fungal species. The analysis of the MAPK gene family resulted in the discovery of several novel activation loop motifs (T-T-Y, T-I-Y, T-N-Y, T-H-Y, T-S-Y, K-G-Y, T-Q-Y, S-E-Y and S-D-Y) in fungal MAPKs. The phylogenetic analysis suggests that fungal MAPKs are non-polymorphic, had evolved from their common ancestors around 1500 million years ago, and are distantly related to plant MAPKs. We are the first to report the presence of nine novel activation loop motifs in fungal MAPKs. The specificity of the activation loop motif plays a significant role in controlling different growth and stress related pathways in fungi. Hence, the presences of these nine novel activation loop motifs in fungi are of special interest. 相似文献
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34.
Anti-cholinesterase hybrids as multi-target-directed ligands against Alzheimer’s disease (1998–2018)
Alzheimer’s disease (AD) is a genetically complex, progressive and irreversible neurodegenerative disorder of the brain which involves multiple associated etiological targets. The complex pathogenesis of AD gave rise to multi-target-directed ligands (MTDLs) principle to combat this dreaded disease. Within this approach, the design and synthesis of hybrids prevailed greatly because of their capability to simultaneously target the intertwined pathogenesis components of the disease. The hybrids include pharmacophoric hybridization of two or more established chemical scaffolds endowed with the desired pharmacological properties into a single moiety. In AD, the primary foundation of medication therapy and drug design strategies includes the inhibition of cholinesterase (ChE) enzymes. Hence the development of ChE inhibition based hybrids is the central choice of AD medicinal chemistry research. To illustrate the progress of ChE inhibition based hybrids and novel targets, we reviewed the medicinal chemistry and pharmacological properties of the multi-target molecules published since 1998-December 2018. We hope that this article will allow the readers to easily follow the evolution of this prominent medicinal chemistry approach to develop a more efficient inhibitor. 相似文献
35.
Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) based on three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were conducted on a series (44 compounds) of diaryloxy-methano-phenanthrene derivatives as potent antitubercular agents. The best predictions were obtained with a CoMFA standard model (q (2)=0.625, r (2)=0.994) and with CoMSIA combined steric, electrostatic, and hydrophobic fields (q (2)=0.486, r (2)=0.986). Both models were validated by a test set of seven compounds and gave satisfactory predictive r (2) values of 0.999 and 0.745, respectively. CoMFA and CoMSIA contour maps were used to analyze the structural features of the ligands to account for the activity in terms of positively contributing physicochemical properties: steric, electrostatic, and hydrophobic fields. The information obtained from CoMFA and CoMSIA 3-D contour maps can be used for further design of phenanthrene-based analogs as anti-TB agents. The resulting contour maps, produced by the best CoMFA and CoMSIA models, were used to identify the structural features relevant to the biological activity in this series of analogs. Further analysis of these interaction-field contour maps also showed a high level of internal consistency. This study suggests that introduction of bulky and highly electronegative groups on the basic amino side chain along with decreasing steric bulk and electronegativity on the phenanthrene ring might be suitable for designing better antitubercular agents. 相似文献
36.
Ansuman Panda Debashis Jena Mrinal Kanti Datta Janmejay Parhi Radhakrishnan Kizhakke Veettil Pramod Kumar Pandey 《Zeitschrift fur angewandte Ichthyologie》2019,35(6):1242-1248
The present study explains the intraspecific variation in Indian Hill trout (Barilius bendelisis) on the basis of image based truss network system and D‐loop region of mtDNA. A total of 210 samples were collected from three different rivers (Teesta, Kameng and Myntudu River) of North East India in Indo‐Burma Biodiversity Hotspot. By using the software applications (tpsDig version 2.1 and PAST), a total of 25 morphometric measurements were generated from 10 landmarks. The Analysis of Variance (ANOVA), Factor Analysis (FA) and Discriminate Function Analysis (DFA) showed, out of the total variations, factor 1 explained 46.74% while factor 2 and factor 3 explained 27.14% and 11.92%, respectively. Using these variables 83.33% of the cross‐validated specimens were classified into distinct groups. Analysis of Molecular Variance (AMOVA) and pairwise Fst value for D‐loop region of mtDNA also showed high to medium level of genetic variation among the stocks and within the stocks. We conclude that the observed discrete stocks might be the result of changing environmental conditions in different rivers of the hotspot as the rivers are present at different altitudinal labels. It is also believed that the variation might be due to the construction of barrages across the river which hinder the mixing among the stocks. 相似文献
37.
Debapriya De Priyanka Chowdhury Sujogya K. Panda Utpal Ghosh 《Journal of cellular biochemistry》2019,120(12):19841-19857
Despite the advancement of the pharmaceutical industry, medicinal plants are still a reliable source of traditional medicines to cure a number of diseases. Various parts of Dillenia pentagyna are used in traditional medicine in India for treatment of various disorders including cancers, but detailed mechanisms are still unknown. Dried leaves of D. pentagyna were extracted with ethanol and termed as an ethanolic extract of leaves of D. pentagyna (EELDP). Our aim was to elucidate the role of EELDP in in-vitro cell migration and apoptosis in highly metastatic human lung adenocarcinoma A549 cells. We measured cell viability and in-vitro cell migration in three different human cancer cells A549, HeLa and U2OS treated with EELDP (0-0.6 mg/mL). However, A549 cells showed higher sensitivity to EELDP treatment. Hence we studied several key markers of metastasis and apoptosis pathway in A549 cells treated with EELDP. EELDP treatment significantly reduced in-vitro cell migration, wound healing, expression and activity of MMP-2, MMP-9 via reduction of nuclear factor kappa Beta (NF-κβ). EELDP also reduced vimentin, N-cadherin and increased claudin-1. The intrinsic pathway of apoptosis was triggered by EELDP via the NF-κβ pathway through the increase of the Bax to Bcl2 ratio, leading to the fall of mitochondrial membrane potential and subsequently induced release of cytochrome c, activation of caspase-3 followed by nuclear fragmentation in A549 cells. Furthermore, we observed change of a few markers of metastasis and apoptosis in other two cell types HeLa and U2OS treated with EELDP. These data implicate that the effect of EELDP is not cell-specific. Since only 0.1 mg/mL EELDP significantly reduces in-vitro cell migration and increases apoptosis, the active compound(s) present in EELDP is very much potent to control highly metastatic cancer. 相似文献
38.
Sunita Panda Ananya Nanda Nilanjan Sahu Deepak K. Ojha Biswaranjan Pradhan Anjali Rai Amol
R. Suryawanshi Nilesh Banavali Sasmita Nayak 《Bioscience reports》2022,42(3)
Inteins are auto-processing domains that implement a multistep biochemical reaction termed protein splicing, marked by cleavage and formation of peptide bonds. They excise from a precursor protein, generating a functional protein via covalent bonding of flanking exteins. We report the kinetic study of splicing and cleavage reaction in [Fe–S] cluster assembly protein SufB from Mycobacterium tuberculosis (Mtu). Although it follows a canonical intein splicing pathway, distinct features are added by extein residues present in the active site. Sequence analysis identified two conserved histidines in the N-extein region; His-5 and His-38. Kinetic analyses of His-5Ala and His-38Ala SufB mutants exhibited significant reductions in splicing and cleavage rates relative to the SufB wildtype (WT) precursor protein. Structural analysis and molecular dynamics (MD) simulations suggested that Mtu SufB displays a unique mechanism where two remote histidines work concurrently to facilitate N-terminal cleavage reaction. His-38 is stabilized by the solvent-exposed His-5, and can impact N–S acyl shift by direct interaction with the catalytic Cys1. Development of inteins as biotechnological tools or as pathogen-specific novel antimicrobial targets requires a more complete understanding of such unexpected roles of conserved extein residues in protein splicing. 相似文献
39.
40.
Regulation and cloning of microbial chitinase genes 总被引:16,自引:0,他引:16
A range of chitinase genes from microorganisms have been cloned and the potential uses of these genetically manipulated organisms
are being investigated by various researchers. Fungi and yeast are better producers of chitinase than bacteria. Since fungi
grow at a slower rate, there have been efforts to clone the fungal chitinase genes into fast-growing bacteria. This review
gives a brief survey of recent progress in the regulation and cloning of microbial chitinase genes. Emphasis is placed on
the post-translational modification and localization of the recombinant protein in the host. Various amino acid domains are
present in this protein. The mode of catalytic activity of the recombinant protein in comparison to the wild-type protein
is discussed in the available literature. The different mechanisms involved in the regulation of chitinase genes from various
microorganisms is discussed by the researchers. The scope of future research and conclusions yet to be obtained in this particular
area are also outlined in this review.
Received: 13 July 1998 / Received revision: 28 October 1998 / Accepted: 30 October 1998 相似文献