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71.
In this study, we characterized a putative peroxidase Prx1 of Candida albicans by: 1) demonstrating the thioredoxin-linked peroxidase activity with purified proteins, 2) examining the sensitivity to several
oxidants and the accumulation of intracellular reactive oxygen species with a null mutant (prx1Δ), a mutant (C69S) with a point mutation at Cys69, and a revertant, and 3) subcelluar localization. Enzymatic assays showed
that Prx1 is a thioredoxin-linked peroxidase which reduces both hydrogen peroxide (H2O2) and tert-butyl hydroperoxide (t-BOOH). Compared with two other strong H2O2 scavenger mutants for TSA1 and CAT1, prx1Δ and C69S were less sensitive to H2O2, menadione and diamide at all concentrations tested, but were more sensitive to low concentration of t-BOOH. Intracellular reactive oxygen species accumulated in prx1Δ and C69S cells treated with t-BOOH but not H2O2. These results suggest that peroxidase activity of Prx1 is specified to t-BOOH in cells. In both biochemical and physiological cases, the evolutionarily conserved Cys69 was found to be essential
for the function. Immunocytochemical staining revealed Prx1 is localized in the cytosol of yeast cells, but is translocated
to the nucleus during the hyphal transition, though the significances of this observation are unclear. Our data suggest that
PRX1 has a thioredoxin peroxidase activity reducing both t-BOOH and H2O2, but its cellular function is specified to t-BOOH. 相似文献
72.
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74.
Mark A. Seefeld Hong Lin Joerg Holenz Dave Downie Brian Donovan Tingting Fu Kishore Pasikanti Wei Zhen Matthew Cato Khuram W. Chaudhary Pat Brady Tania Bakshi Dwight Morrow Sridharan Rajagopal Swapan Kumar Samanta Naveena Madhyastha Bharathi Mohan Kuppusamy Robert W. Dougherty Yasuji Matsuoka 《Bioorganic & medicinal chemistry letters》2018,28(23-24):3793-3797
Neuronal voltage-gated potassium channels, KV7s, are the molecular mediators of the M current and regulate membrane excitability in the central and peripheral neuronal systems. Herein, we report novel small molecule KV7 openers that demonstrate anti-seizure activities in electroshock and pentylenetetrazol-induced seizure models without influencing Rotarod readouts in mice. The anti-seizure activity was determined to be proportional to the unbound concentration in the brain. KV7 channels are also expressed in the bladder smooth muscle (detrusor) and activation of these channels may cause localized undesired effects. Therefore, the impact of individual KV7 isoforms was investigated in human detrusor tissue using a panel of KV7 openers with distinct activity profiles among KV7 isoforms. KCNQ4 and KCNQ5 mRNA were highly expressed in detrusor tissue, yet a compound that has significantly reduced activity on homomeric KV7.4 did not reduce detrusor contraction. This may suggest that the homomeric KV7.4 channel plays a less significant role in bladder contraction and further investigation is needed. 相似文献
75.
T Bhaskar Kumar Ch Sumanth S Vaishaly M Srinivasa Rao KB Chandra Sekhar CL Meda A Kandale D Rambabu G Rama Krishna C Malla Reddy K Shiva Kumar KV Parsa M Pal 《Bioorganic & medicinal chemistry letters》2012,22(17):5639-5647
Novel polysubstituted pyrroles have been designed and accessed via a one-pot multicomponent reaction followed by Pd-mediated C-C bond forming reactions. All the compounds synthesized were tested for their PDE4B inhibitory properties in vitro and two of them obtained via Heck reaction showed significant inhibition. The docking results suggested that these alkenyl derivatives containing ester moiety interact well with the PDE4B protein in silico where the ester carbonyl oxygen played a key role. The pyrrole framework presented here could be a new template for the identification of small molecule based novel inhibitors of PDE4. The single crystal X-ray data of a representative compound is presented. 相似文献
76.
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Srinivasa T. Reddy Mohamad Navab G.M. Anantharamaiah Alan M. Fogelman 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2014,1841(1):162-167
Despite strong evidence that HDL-cholesterol levels predict atherosclerotic events in a population, attempts at using an HDL-based treatment strategy have not yet been successful. Most of the efforts to date have focused on raising plasma HDL-cholesterol levels. This brief review focuses on a different strategy, which is based on the use of 18-amino acid apoA-I mimetic peptides. The story of these peptides spans decades and illustrates the remarkable complexity of HDL-based treatment strategies, but suggests that such a strategy may still be successful. 相似文献
78.
Justin N. Vaughn Srinivasa R. Chaluvadi Tushar Latha Rangan Jeffrey L. Bennetzen 《PloS one》2014,9(10)
Plants from the Zingiberaceae family are a key source of spices and herbal medicines. Species identification within this group is critical in the search for known and possibly novel bioactive compounds. To facilitate precise characterization of this group, we have sequenced chloroplast genomes from species representing five major groups within Zingiberaceae. Generally, the structure of these genomes is similar to the basal angiosperm excepting an expansion of 3 kb associated with the inverted repeat A region. Portions of this expansion appear to be shared across the entire Zingiberales order, which includes gingers and bananas. We used whole plastome alignment information to develop DNA barcodes that would maximize the ability to differentiate species within the Zingiberaceae. Our computation pipeline identified regions of high variability that were flanked by highly conserved regions used for primer design. This approach yielded hitherto unexploited regions of variability. These theoretically optimal barcodes were tested on a range of species throughout the family and were found to amplify and differentiate genera and, in some cases, species. Still, though these barcodes were specifically optimized for the Zingiberaceae, our data support the emerging consensus that whole plastome sequences are needed for robust species identification and phylogenetics within this family. 相似文献
79.
Ajith Anand Chaluvadi Srinivasa Rao 《In vitro cellular & developmental biology. Plant》2000,36(1):61-64
Summary A protocol is described for rapid multiplication of Piper barberi Gamble (Piperaceae) through shoot tip and nodal explant cultures. Nodal explants with a single axillary meristem showed three
times better response with respect to shoot proliferation when compared to shoot tip explants. The best shoot proliferation
response of nodal explants was observed with a cytokinin combination of N6-benzyladenine (4.43 μM) and kinetin (2.32 μM), with 88% bud break. The number of shoot initials (2.4) produced per nodal explant was twice the number of shoot initials
(1.2) per shoot tip. An average of 6.9±0.58 adventitious shoots were observed from the proximal end of the internodal explants
on Mursashige and Skoog (1962) (Ms) basal medium supplemented with N6-benzyladenine (2.22 μM) and kinetin (0.46 μM). A multiplication rate of 82 shoots per explant could be achieved after 9 wk of subculturing. The in vitro shoots were rooted on one-half and one-quarter MS basal medium. The shoots rooted on one-quarter MS in the dark produced
eight roots with an average root length of 3.36 cm and 98% survival. These plants were transferred to the field with a survival
rate of 75%. 相似文献
80.
Characterization of a novel and specific inhibitor for the pro-apoptotic protease Omi/HtrA2 总被引:10,自引:0,他引:10
Cilenti L Lee Y Hess S Srinivasula S Park KM Junqueira D Davis H Bonventre JV Alnemri ES Zervos AS 《The Journal of biological chemistry》2003,278(13):11489-11494
Omi/HtrA2 is a mammalian serine protease with high homology to bacterial HtrA chaperones. Omi/HtrA2 is localized in mitochondria and is released to the cytoplasm in response to apoptotic stimuli. Omi/HtrA2 induces cell death in a caspase-dependent manner by interacting with the inhibitor of apoptosis protein as well as in a caspase-independent manner that relies on its protease activity. We describe the identification and characterization of a novel compound as a specific inhibitor of the proteolytic activity of Omi/HtrA2. This compound (ucf-101) was isolated in a high throughput screening of a combinatorial library using bacterially made Omi-(134-458) protease and fluorescein-casein as a generic substrate. ucf-101 showed specific activity against Omi/HtrA2 and very little activity against various other serine proteases. This compound has a natural fluorescence that was used to monitor its ability to enter mammalian cells. ucf-101, when tested in caspase-9 (-/-) null fibroblasts, was found to inhibit Omi/HtrA2-induced cell death. 相似文献