全文获取类型
收费全文 | 242篇 |
免费 | 16篇 |
专业分类
258篇 |
出版年
2023年 | 1篇 |
2022年 | 6篇 |
2021年 | 4篇 |
2020年 | 5篇 |
2019年 | 1篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 7篇 |
2015年 | 18篇 |
2014年 | 13篇 |
2013年 | 15篇 |
2012年 | 21篇 |
2011年 | 21篇 |
2010年 | 18篇 |
2009年 | 11篇 |
2008年 | 22篇 |
2007年 | 11篇 |
2006年 | 10篇 |
2005年 | 10篇 |
2004年 | 13篇 |
2003年 | 7篇 |
2002年 | 6篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 1篇 |
1997年 | 3篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1976年 | 3篇 |
1973年 | 1篇 |
1970年 | 2篇 |
排序方式: 共有258条查询结果,搜索用时 0 毫秒
191.
Prabhakaran Vasantha-Srinivasan Sridhar Shanmuga-Priya Yeon Soo Han Narayanaswamy Radhakrishnan Kesavan Amala Sengodan Karthi Sengottayan Senthil-Nathan 《Entomological Research》2023,53(11):485-508
Extracts of botanical origin naturally contain a complex mixture of chemicals considered effective in managing lepidopteran pests. Chemical screening of the ethanolic leaf extracts of two fig tree species, Ficus lyrata and Ficus auriculata, delivered 12 and 15 phyto-compounds with relatively high peak area percentages in phytol and flavone, respectively. Larvicidal activity against Spodoptera litura yielded higher mortality rates at maximum-concentration treatment (600 ppm) with Ficus lyrata (91.3%) and Ficus auriculata (98.5%) extracts during the second instar. Sub-lethal dosages (300 ppm) of both Ficus lyrata and Ficus auriculata extracts impeded the development and reproduction of lepidopteran pests. The enzyme-inhibition activity of both fig extracts elicited a significant reduction in the major digestive enzymes alkaline phosphatase, acid phosphatase, and lactate dehydrogenase dose-responsively. Mid-gut histological screening of Ficus lyrata and Ficus auriculata extracts displayed gut lumen disruptions, shape alterations of columnar cells, and brush-border membrane damage. Further, the non-target toxicity of fig extracts against the red worm Eisenia foetida was minimal compared with that of the chemical temephos. Overall, the Ficus extracts proved to be eco-friendly strategies for managing the polyphagous pest Spodoptera litura and are potentially more sustainable and less harmful to non-target earthworms. Nonetheless, in silico predictions suggest that the active compounds in fig extracts are predominantly toxic against honeybees (16 compounds) and violate TICE rules (10 compounds). Therefore, the biological actions of fig extracts' individual novel chemistries need to be examined on target and non-target species to develop better pest management strategies. 相似文献
192.
Thankappan UP Madhusudana SN Desai A Jayamurugan G Rajesh YB Jayaraman N 《Bioconjugate chemistry》2011,22(2):115-119
The nonviral vector based gene delivery approach is attractive due to advantages associated with molecular-level modifications suitable for optimization of vector properties. In a new class of nonviral gene delivery systems, we herein report the potential of poly(ether imine) (PETIM) dendrimers to mediate an effective gene delivery function. PETIM dendrimer, constituted with tertiary amine branch points, n-propyl ether linkers and primary amines at their peripheries, exhibits significantly reduced toxicities, over a broad concentration range. The dendrimer complexes pDNA effectively, protects DNA from endosomal damages, and delivers to the cell nucleus. Gene transfection studies, utilizing a reporter plasmid pEGFP-C1 and upon complexation with dendrimer, showed a robust expression of the encoded protein. The study shows that PETIM dendrimers are hitherto unknown novel gene delivery vectors, combining features of poly(ethylene imine)-based polymers and dendrimers, yet are relatively nontoxic and structurally precise. 相似文献
193.
Sabet NS Subramaniam G Navaratnam P Sekaran SD 《Journal of microbiological methods》2007,68(1):157-162
In this study we describe a triplex real-time PCR assay that enables the identification of S. aureus and detection of two important antibiotic resistant genes simultaneously using real-time PCR technology in a single assay. In this triplex real-time PCR assay, the mecA (methicillin resistant), femA (species specific S. aureus) and aacA-aphD (aminoglycoside resistant) genes were detected in a single test using dual-labeled Taqman probes. The assay gives simultaneous information for the identification of S. aureus and detection of methicillin and aminoglycoside resistance in staphylococcal isolates. 152 clinical isolates were subjected to this triplex real-time PCR assay. The results of the triplex real-time PCR assay correlated with the results of the phenotypic antibiotic susceptibility testing. The results obtained from triplex real-time PCR assay shows that the primer and probe sets were specific for the identification of S. aureus and were able to detect methicillin- and aminoglycoside-resistant genes. The entire assay can be performed within 3 h which is a very rapid method that can give simultaneous information for the identification of S. aureus and antibiotic resistance pattern of a staphylococcal isolate. The application of this rapid method in microbiology laboratories would be a valuable tool for the rapid identification of the S. aureus isolates and determination of their antibiotic resistance pattern with regards to methicillin and aminoglycosides. 相似文献
194.
Rohini Narayanaswamy Vignesh Iyer Prachi Khare Mary Lou Bodziak Darlene Badgett Robert Zivadinov Bianca Weinstock-Guttman Todd C. Rideout Murali Ramanathan Richard W. Browne 《PloS one》2015,10(4)
Background
Oxysterols are promising biomarkers of neurodegenerative diseases that are linked with cholesterol and vitamin D metabolism. There is an unmet need for methods capable of sensitive, and simultaneous quantitation of multiple oxysterols, vitamin D and cholesterol pathway biomarkers.Methods
A method for simultaneous determination of 5 major oxysterols, 25-hydroxy vitamin D3 and cholesterol in human plasma was developed. Total oxysterols were prepared by room temperature saponification followed by solid phase extraction from plasma spiked with deuterated internal standards. Oxysterols were resolved by reverse phase HPLC using a methanol/water/0.1% formic acid gradient. Oxysterols and 25-hydroxy vitamin D3 were detected with atmospheric pressure chemical ionization mass spectrometry in positive ion mode; in-series photodiode array detection at 204nm was used for cholesterol. Method validation studies were performed. Oxysterol levels in 220 plasma samples from healthy control subjects, multiple sclerosis and other neurological disorders patients were quantitated.Results
Our method quantitated 5 oxysterols, cholesterol and 25-hydroxy vitamin D3 from 200 μL plasma in 35 minutes. Recoveries were >85% for all analytes and internal standards. The limits of detection were 3-10 ng/mL for oxysterols and 25-hydroxy vitamin D3 and 1 μg/mL for simultaneous detection of cholesterol. Analytical imprecision was <10 %CV for 24(S)-, 25-, 27-, 7α-hydroxycholesterol (HC) and cholesterol and ≤15 % for 7-keto-cholesterol. Multiple Sclerosis and other neurological disorder patients had lower 27-hydroxycholesterol levels compared to controls whereas 7α-hydroxycholesterol was lower specifically in Multiple Sclerosis.Conclusion
The method is suitable for measuring plasma oxysterols levels in human health and disease. Analysis of human plasma indicates that the oxysterol, bile acid precursors 7α-hydroxycholesterol and 27-hydroxycholesterol are lower in Multiple Sclerosis and may serve as potential biomarkers of disease. 相似文献195.
Balasubramanian Lakshmi Madhulika Mishra Narayanaswamy Srinivasan Govindaraju Archunan 《PloS one》2015,10(8)
Lipocalins constitute a superfamily of extracellular proteins that are found in all three kingdoms of life. Although very divergent in their sequences and functions, they show remarkable similarity in 3-D structures. Lipocalins bind and transport small hydrophobic molecules. Earlier sequence-based phylogenetic studies of lipocalins highlighted that they have a long evolutionary history. However the molecular and structural basis of their functional diversity is not completely understood. The main objective of the present study is to understand functional diversity of the lipocalins using a structure-based phylogenetic approach. The present study with 39 protein domains from the lipocalin superfamily suggests that the clusters of lipocalins obtained by structure-based phylogeny correspond well with the functional diversity. The detailed analysis on each of the clusters and sub-clusters reveals that the 39 lipocalin domains cluster based on their mode of ligand binding though the clustering was performed on the basis of gross domain structure. The outliers in the phylogenetic tree are often from single member families. Also structure-based phylogenetic approach has provided pointers to assign putative function for the domains of unknown function in lipocalin family. The approach employed in the present study can be used in the future for the functional identification of new lipocalin proteins and may be extended to other protein families where members show poor sequence similarity but high structural similarity. 相似文献
196.
197.
Arangasamy Yazhini Das Swayam Prakash Sidhanta Narayanaswamy Srinivasan 《Bioinformation》2021,17(3):439
Mutations in the spike protein of SARS-CoV-2 are the major causes for the modulation of ongoing COVID-19 infection. Currently, the D614G substitution in the spike protein has become dominant worldwide. It is associated with higher infectivity than the ancestral (D614)variant. We demonstrate using Gaussian network model-based normal mode analysis that the D614G substitution occurs at the hinge region that facilitates domain-domain motions between receptor binding domain and S2 region of the spike protein. Computer-aided mutagenesis and inter-residue energy calculations reveal that contacts involving D614 are energetically frustrated. However, contacts involving G614 are energetically favourable, implying the substitution strengthens residue contacts that are formed within as well as between protomers. We also find that the free energy difference (ΔΔG) between two variants is -2.6 kcal/mol for closed and -2.0 kcal/mol for 1-RBD up conformation. Thus, the thermodynamic stability has increased upon D614G substitution. Whereas the reverse mutation in spike protein structures having G614 substitution has resulted in the free energy differences of 6.6 kcal/mol and 6.3 kcal/mol for closed and 1-RBD up conformations, respectively, indicating that the overall thermodynamic stability has decreased. These results suggest that the D614G substitution modulates the flexibility of spike protein and confers enhanced thermodynamic stability irrespective of conformational states. This data concurs with the known information demonstrating increased availability of the functional form of spikeprotein trimer upon D614G substitution. 相似文献
198.
Anne-Marie Hansen Raghothama Chaerkady Jyoti Sharma J. Javier Díaz-Mejía Nidhi Tyagi Santosh Renuse Harrys K. C. Jacob Sneha M. Pinto Nandini A. Sahasrabuddhe Min-Sik Kim Bernard Delanghe Narayanaswamy Srinivasan Andrew Emili James B. Kaper Akhilesh Pandey 《PLoS pathogens》2013,9(6)
While phosphotyrosine modification is an established regulatory mechanism in eukaryotes, it is less well characterized in bacteria due to low prevalence. To gain insight into the extent and biological importance of tyrosine phosphorylation in Escherichia coli, we used immunoaffinity-based phosphotyrosine peptide enrichment combined with high resolution mass spectrometry analysis to comprehensively identify tyrosine phosphorylated proteins and accurately map phosphotyrosine sites. We identified a total of 512 unique phosphotyrosine sites on 342 proteins in E. coli K12 and the human pathogen enterohemorrhagic E. coli (EHEC) O157:H7, representing the largest phosphotyrosine proteome reported to date in bacteria. This large number of tyrosine phosphorylation sites allowed us to define five phosphotyrosine site motifs. Tyrosine phosphorylated proteins belong to various functional classes such as metabolism, gene expression and virulence. We demonstrate for the first time that proteins of a type III secretion system (T3SS), required for the attaching and effacing (A/E) lesion phenotype characteristic for intestinal colonization by certain EHEC strains, are tyrosine phosphorylated by bacterial kinases. Yet, A/E lesion and metabolic phenotypes were unaffected by the mutation of the two currently known tyrosine kinases, Etk and Wzc. Substantial residual tyrosine phosphorylation present in an etk wzc double mutant strongly indicated the presence of hitherto unknown tyrosine kinases in E. coli. We assess the functional importance of tyrosine phosphorylation and demonstrate that the phosphorylated tyrosine residue of the regulator SspA positively affects expression and secretion of T3SS proteins and formation of A/E lesions. Altogether, our study reveals that tyrosine phosphorylation in bacteria is more prevalent than previously recognized, and suggests the involvement of phosphotyrosine-mediated signaling in a broad range of cellular functions and virulence. 相似文献
199.
Background
Dengue infection ranks as one of the most significant viral diseases of the globe. Currently, there is no specific vaccine or antiviral therapy for prevention or treatment. Monocytes/macrophages are the principal target cells for dengue virus and are responsible for disseminating the virus after its transmission. Dengue virus enters target cells via receptor-mediated endocytosis after the viral envelope protein E attaches to the cell surface receptor. This study aimed to investigate the effect of silencing the CD-14 associated molecule and clathrin-mediated endocytosis using siRNA on dengue virus entry into monocytes.Methodology/Principal Findings
Gene expression analysis showed a significant down-regulation of the target genes (82.7%, 84.9 and 76.3% for CD-14 associated molecule, CLTC and DNM2 respectively) in transfected monocytes. The effect of silencing of target genes on dengue virus entry into monocytes was investigated by infecting silenced and non-silenced monocytes with DENV-2. Results showed a significant reduction of infected cells (85.2%), intracellular viral RNA load (73.0%), and extracellular viral RNA load (63.0%) in silenced monocytes as compared to non-silenced monocytes.Conclusions/Significance
Silencing the cell surface receptor and clathrin mediated endocytosis using RNA interference resulted in inhibition of the dengue virus entry and subsequently multiplication of the virus in the monocytes. This might serve as a novel promising therapeutic target to attenuate dengue infection and thus reduce transmission as well as progression to severe dengue hemorrhagic fever. 相似文献200.