全文获取类型
收费全文 | 214篇 |
免费 | 19篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 15篇 |
2020年 | 8篇 |
2019年 | 3篇 |
2018年 | 8篇 |
2017年 | 9篇 |
2016年 | 8篇 |
2015年 | 12篇 |
2014年 | 11篇 |
2013年 | 11篇 |
2012年 | 24篇 |
2011年 | 18篇 |
2010年 | 9篇 |
2009年 | 4篇 |
2008年 | 6篇 |
2007年 | 14篇 |
2006年 | 12篇 |
2005年 | 4篇 |
2004年 | 8篇 |
2003年 | 4篇 |
2002年 | 4篇 |
2001年 | 6篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1992年 | 2篇 |
1991年 | 5篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1982年 | 2篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有233条查询结果,搜索用时 93 毫秒
71.
Virulence targeted inhibitory effect of linalool against the exclusive uropathogen Proteus mirabilis
Ravindran Durgadevi Rajaiah Alexpandi Thirukannamangai Krishnan Swetha Gurusamy Abirami Selvam Vishnu 《Biofouling》2013,29(5):508-525
Proteus mirabilis is one of the leading causes of catheter-associated UTIs (CAUTI) in individuals with prolonged urinary catheterization. Since, biofilm assisted antibiotic resistance is reported to complicate the treatment strategies of P. mirabilis infections, the present study was aimed to attenuate biofilm and virulence factor production in P. mirabilis. Linalool is a naturally occurring monoterpene alcohol found in a wide range of flowers and spice plants and has many biological applications. In this study, linalool exhibited concentration dependent anti-biofilm activity against crystalline biofilm of P. mirabilis through reduced production of the virulence enzyme urease that raises the urinary pH and drives the formation of crystals (struvite) in the biofilm. The results of q-PCR analysis unveiled the down regulation of biofilm/virulence associated genes upon linalool treatment, which was in correspondence with the in vitro bioassays. Thus, this study reports the feasibility of linalool acting as a promising anti-biofilm agent against P. mirabilis mediated CAUTI. 相似文献
72.
Khursigara CM Lan G Neumann S Wu X Ravindran S Borgnia MJ Sourjik V Milne J Tu Y Subramaniam S 《The EMBO journal》2011,30(9):1719-1729
In chemotactic bacteria, transmembrane chemoreceptors, CheA and CheW form the core signalling complex of the chemotaxis sensory apparatus. These complexes are organized in extended arrays in the cytoplasmic membrane that allow bacteria to respond to changes in concentration of extracellular ligands via a cooperative, allosteric response that leads to substantial amplification of the signal induced by ligand binding. Here, we have combined cryo-electron tomographic studies of the 3D spatial architecture of chemoreceptor arrays in intact E. coli cells with computational modelling to develop a predictive model for the cooperativity and sensitivity of the chemotaxis response. The predictions were tested experimentally using fluorescence resonance energy transfer (FRET) microscopy. Our results demonstrate that changes in lateral packing densities of the partially ordered, spatially extended chemoreceptor arrays can modulate the bacterial chemotaxis response, and that information about the molecular organization of the arrays derived by cryo-electron tomography of intact cells can be translated into testable, predictive computational models of the chemotaxis response. 相似文献
73.
Saha S Mondal S Ravindran R Bhowmick S Modak D Mallick S Rahman M Kar S Goswami R Guha SK Pramanik N Saha B Ali N 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(8):5592-5603
Visceral leishmaniasis (VL) or kala-azar is known to be associated with a mixed Th1-Th2 response, and effective host defense requires the induction of IFN-gamma and IL-12. We address the role of the differential decline of IL-10 and TGF-beta in response to sodium antimony gluconate (SAG) and amphotericin B (AmB), the therapeutic success of SAG and AmB in Indian VL, and the significance of IL-10 and TGF-beta in the development and progression of post-kazla-azar dermal leishmaniasis (PKDL). In the active disease, PBMC from VL patients showed suppressed Ag-specific lymphoproliferation, IFN-gamma and IL-12 production, and elevation of IL-10 and TGF-beta. Cure corresponded with an elevation in IFN-gamma and IL-12 production and down-regulation of IL-10 and TGF-beta. Both CD4(+) and CD8(+) T cells were involved in IFN-gamma and IL-10 production. Interestingly, the retention and maintenance of residual IL-10 and TGF-beta in some SAG-treated individuals and the elevation of IL-10 and TGF-beta in PKDL, a sequel to kala-azar, probably reflects the role of these cytokines in reactivation of the disease in the form of PKDL. Contrastingly, AmB treatment of VL resulted in negligible TGF-beta levels and absolute elimination of IL-10, reflecting the better therapeutic activity of AmB and its probable role in the recent decline in PKDL occurrences in India. Moreover, elucidation of immune responses in Indian PKDL patients revealed a spectral pattern of disease progression where disease severity could be correlated inversely with lymphoproliferation and directly with TGF-beta, IL-10, and Ab production. In addition, the enhancement of CD4(+)CD25(+) T cells in active VL, their decline at cure, and reactivation in PKDL suggest their probable immunosuppressive role in these disease forms. 相似文献
74.
Identification of Pseudomonas syringae pv. syringae 61 type III secretion system Hrp proteins that can travel the type III pathway and contribute to the translocation of effector proteins into plant cells
下载免费PDF全文
![点击此处可从《Journal of bacteriology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ramos AR Morello JE Ravindran S Deng WL Huang HC Collmer A 《Journal of bacteriology》2007,189(15):5773-5778
Pseudomonas syringae translocates effector proteins into plant cells via an Hrp1 type III secretion system (T3SS). T3SS components HrpB, HrpD, HrpF, and HrpP were shown to be pathway substrates and to contribute to elicitation of the plant hypersensitive response and to translocation and secretion of the model effector AvrPto1. 相似文献
75.
76.
Expression profiling of human immune cell subsets identifies miRNA-mRNA regulatory relationships correlated with cell type specific expression 总被引:1,自引:0,他引:1
77.
Aditya K Panda Jyoti R Parida Rina Tripathy Sarit S Pattanaik Balachandran Ravindran Bidyut K Das 《Arthritis research & therapy》2012,14(5):R218
Introduction
A role for mannose binding lectin (MBL) in autoimmune diseases has been demonstrated earlier and elevated level of MBL has been shown in systemic lupus erythematosus (SLE) patients. In the current study, we investigated MBL as a potential biomarker for disease activity in SLE.Methods
In a case control study SLE patients (93 females) and 67 age, sex, ethnicity matched healthy controls were enrolled. Plasma MBL levels were quantified by enzyme linked immunosorbent assay (ELISA). Clinical, serological and other markers of disease activity (C3, C4 and anti-dsDNA) were measured by standard laboratory procedures.Results
Plasma MBL levels were significantly high in SLE patients compared to healthy controls (P < 0.0001). MBL levels were variable in different clinical categories of SLE. Lower levels were associated with musculoskeletal and cutaneous manifestations (P = 0.002), while higher and intermediate MBL levels were significantly associated with nephritis in combination with other systemic manifestations (P = 0.01 and P = 0.04 respectively). Plasma MBL correlated with systemic lupus erythematosus disease activity index (SLEDAI) (P = 0.0003, r = 0.36), anti-dsDNA (P < 0.0001, r = 0.54), proteinuria (P < 0.0001, r = 0.42) and negatively correlated with C3 (P = 0.007, r = -0.27) and C4 (P = 0.01, r = -0.29).Conclusions
Plasma MBL is a promising marker in the assessment of SLE disease activity. 相似文献78.
Geeta R Ramnath RL Rao HS Chandra V 《Biochemical and biophysical research communications》2008,373(2):258-264
We report the generation of functional dopaminergic neurons from human embryonic stem cells (hESCs) using a growth factor mediated multistep EB protocol and its therapeutic effects in vivo. Embryoid bodies (EBs) were cultured in insulin-transferrin-selenium fibronectin (ITSFn) media for the selection of neural precursor cells (NPC). The selected cells on exposure to N2 media supplemented with EGF, bFGF initially aggregated to generate spontaneous free floating neurospheres and on exposure to signaling molecules Shh and FGF-8 differentiated into dopaminergic neurons (40% TH+ cells/total neurons). The differentiated NPC expressed dopaminergic specific markers both at cellular and molecular levels. They secreted detectable levels of dopamine into the culture supernatant. The most unique feature of our protocol is the generation of free floating neurospheres which can be expanded for a longer period without losing their capability to differentiate into DA neurons. Further, transplantation of NPCs into the substantia nigra of 6-OHDA lesioned rat model of Parkinson’s disease elicited significant reversal of lesion induced motor deficits which was sustained upto the end of 1 year long study period. Immunohistochemical studies of the grafted area one year post transplantation revealed that transplanted hESC derived neural precursor cells survived, integrated in vivo and differentiated into dopaminergic neurons without teratoma formation.In summary, our results encourage the potential use of hESC derived dopaminergic neurons for future clinical application in Parkinson’s disease. 相似文献
79.
Lao QZ Kobrinsky E Harry JB Ravindran A Soldatov NM 《The Journal of biological chemistry》2008,283(23):15577-15588
Ca(v)beta subunits support voltage gating of Ca(v)1.2 calcium channels and play important role in excitation-contraction coupling. The common central membrane-associated guanylate kinase (MAGUK) region of Ca(v)beta binds to the alpha-interaction domain (AID) and the IQ motif of the pore-forming alpha(1C) subunit, but these two interactions do not explain why the cardiac Ca(v)beta(2) subunit splice variants differentially modulate inactivation of Ca(2+) currents (I(Ca)). Previously we described beta(2Deltag), a functionally active splice variant of human Ca(v)beta(2) lacking MAGUK. By deletion analysis of beta(2Deltag), we have now identified a 41-amino acid C-terminal essential determinant (beta(2)CED) that stimulates I(Ca) in the absence of Ca(v)beta subunits and conveys a +20-mV shift in the peak of the I(Ca)-voltage relationship. The beta(2)CED is targeted by alpha(1C) to the plasma membrane, forms a complex with alpha(1C) but does not bind to AID. Electrophysiology and binding studies point to the calmodulin-interacting LA/IQ region in the alpha(1C) subunit C terminus as a functionally relevant beta(2)CED binding site. The beta(2)CED interacts with LA/IQ in a Ca(2+)- and calmodulin-independent manner and need LA, but not IQ, to activate the channel. Deletion/mutation analyses indicated that each of the three Ca(v)beta(2)/alpha(1C) interactions is sufficient to support I(Ca). However, beta(2)CED does not support Ca(2+)-dependent inactivation, suggesting that interactions of MAGUK with AID and IQ are crucial for Ca(2+)-induced inactivation. The beta(2)CED is conserved only in Ca(v)beta(2) subunits. Thus, beta(2)CED constitutes a previously unknown integrative part of the multifactorial mechanism of Ca(v)beta(2)-subunit differential modulation of the Ca(v)1.2 calcium channel that in beta(2Deltag) occurs without MAGUK. 相似文献
80.
RAD sequencing reveals genomewide divergence between independent invasions of the European green crab (Carcinus maenas) in the Northwest Atlantic
下载免费PDF全文
![点击此处可从《Ecology and evolution》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Nicholas W. Jeffery Claudio DiBacco Mallory Van Wyngaarden Lorraine C. Hamilton Ryan R. E. Stanley Renée Bernier Jennifer FitzGerald K. Matheson C. H. McKenzie Praveen Nadukkalam Ravindran Robert Beiko Ian R. Bradbury 《Ecology and evolution》2017,7(8):2513-2524
Genomic studies of invasive species can reveal both invasive pathways and functional differences underpinning patterns of colonization success. The European green crab (Carcinus maenas) was initially introduced to eastern North America nearly 200 years ago where it expanded northwards to eastern Nova Scotia. A subsequent invasion to Nova Scotia from a northern European source allowed further range expansion, providing a unique opportunity to study the invasion genomics of a species with multiple invasions. Here, we use restriction‐site‐associated DNA sequencing‐derived SNPs to explore fine‐scale genomewide differentiation between these two invasions. We identified 9137 loci from green crab sampled from 11 locations along eastern North America and compared spatial variation to mitochondrial COI sequence variation used previously to characterize these invasions. Overall spatial divergence among invasions was high (pairwise FST ~0.001 to 0.15) and spread across many loci, with a mean FST ~0.052 and 52% of loci examined characterized by FST values >0.05. The majority of the most divergent loci (i.e., outliers, ~1.2%) displayed latitudinal clines in allele frequency highlighting extensive genomic divergence among the invasions. Discriminant analysis of principal components (both neutral and outlier loci) clearly resolved the two invasions spatially and was highly correlated with mitochondrial divergence. Our results reveal extensive cryptic intraspecific genomic diversity associated with differing patterns of colonization success and demonstrates clear utility for genomic approaches to delineating the distribution and colonization success of aquatic invasive species. 相似文献