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151.
Rajeevkumar Raveendran Sudarsana Devi Suma Priya Madhavan Mayadevi Mathew Steephan Thankayyan R. Santhoshkumar John Cheriyan Rajendran Sanalkumar Kurup K. Pradeep Jackson James Ramakrishnapillai V. Omkumar 《Journal of neurochemistry》2009,110(1):92-105
Ca2+ influx through NMDA-type glutamate receptor at excitatory synapses causes activation of post-synaptic Ca2+ /calmodulin-dependent protein kinase type II (CaMKII) and its translocation to the NR2B subunit of NMDA receptor. The major binding site for CaMKII on NR2B undergoes phosphorylation at Ser1303, in vivo . Even though some regulatory effects of this phosphorylation are known, the mode of dephosphorylation of NR2B-Ser1303 is still unclear. We show that phosphorylation status at Ser1303 enables NR2B to distinguish between the Ca2+ /calmodulin activated form and the autonomously active Thr286-autophosphorylated form of CaMKII. Green fluorescent protein–α-CaMKII co-expressed with NR2B sequence in human embryonic kidney 293 cells was used to study intracellular binding between the two proteins. Binding in vitro was studied by glutathione- S -transferase pull-down assay. Thr286-autophosphorylated α-CaMKII or the autophosphorylation mimicking mutant, T286D-α-CaMKII, binds NR2B sequence independent of Ca2+ /calmodulin unlike native wild-type α-CaMKII. We show enhancement of this binding by Ca2+ /calmodulin. Phosphorylation or a phosphorylation mimicking mutation on NR2B (NR2B-S1303D) abolishes the Ca2+ /calmodulin-independent binding whereas it allows the Ca2+ /calmodulin-dependent binding of α-CaMKII in vitro . Similarly, the autonomously active mutants, T286D-α-CaMKII and F293E/N294D-α-CaMKII, exhibited Ca2+ -independent binding to non-phosphorylatable mutant of NR2B under intracellular conditions. We also show for the first time that phosphatases in the brain such as protein phosphatase 1 and protein phosphatase 2A dephosphorylate phospho-Ser1303 on NR2B. 相似文献
152.
153.
Suganthy N Pandian SK Devi KP 《Journal of enzyme inhibition and medicinal chemistry》2009,24(3):702-707
Alzheimer's disease is a progressive neurodegenerative illness accounting for approximately 50% of all types of dementia in elderly people. The only symptomatic treatment proven effective to date is the use of cholinesterase inhibitors to augment surviving cholinergic activity. The purpose of this study is to investigate cholinesterase inhibitory activity of mangroves as an alternative medicine for the treatment of Alzheimer's disease. About nine mangrove plants, which were used as folk medicine in tropical countries, were collected from Parangipettai, Vellar estuary, Tamilnadu, India. Nile Tilapia muscle homogenate was used as source of enzyme. Inhibitory effect of methanolic leaf extract was assessed under in vitro condition by incubating various concentration of the extract with total cholinesterase and butyryl cholinesterase and assessing their residual activities by Ellman's colorimetric method. The results showed that of the nine plants screened Rhizophora lamarckii, Suaeda monica, Avicennia officinalis and Sesuvium portulacastrum showed 50% inhibitory activity to both TChE and BChE at concentrations less than 2 mg/mL when compared to other plant extracts, which was comparable to the standard drug Donepezil. Phytochemical analysis showed the presence of alkaloids in high concentration which might be correlated to its cholinesterase inhibitory activity. 相似文献
154.
Effect of Cyclodextrin Complexation of Curcumin on its Solubility and Antiangiogenic and Anti-inflammatory Activity in Rat Colitis Model 总被引:2,自引:0,他引:2
The purpose of the study was to prepare and evaluate the anti-inflammatory activity of cyclodextrin (CD) complex of curcumin
for the treatment of inflammatory bowel disease (IBD) in colitis-induced rat model. Inclusion complexes of curcumin were prepared
by common solvent and kneading methods. These complexes were further evaluated for increase in solubility of poorly soluble
curcumin. The inclusion complexes were characterized for enhancement in solubility, in vitro dissolution, surface morphology, infrared, differential scanning calorimetry, and X-ray studies. Solubility, phase solubility,
and in vitro dissolution studies showed that curcumin has higher affinity for hydroxypropyl-β-CD (HPβCD) than other CDs. HPβCD complex
of curcumin was further investigated for its antiangiogenic and anti-inflammatory activity using chick embryo and rat colitis
model. HPβCD complex of curcumin proved to be a potent angioinhibitory compound, as demonstrated by inhibition of angiogenesis
in chorioallantoic membrane assay. Curcumin- and HPβCD-treated rats showed a faster weight gain compared to dextran sulfate
solution (DSS) controls. Whole colon length appeared to be significantly longer in HPβCD-treated rats than pure curcumin and
DSS controls. An additional finding in the DSS-treated rats was the predominance of eosinophils in the chronic cell infiltrate.
Decreased mast cell numbers in the mucosa of the colon of CD of curcumin- and pure-curcumin-treated rats was observed. This
study concluded that the degree of colitis caused by administration of DSS was significantly attenuated by CD of curcumin.
Being a nontoxic natural dietary product, curcumin could be useful in the therapeutic strategy for IBD patients. 相似文献
155.
The ratio of gelatin to sodium carboxymethyl cellulose (SCMC) at which maximum yield was obtained was optimized. This optimized
ratio of gelatin to SCMC along with other parameters was used to prepare microparticles of different sizes. Vegetable oil
was used as emulsion medium. Effect of various factors like amount of surfactant, concentration of polymer on the formation,
and size of the microparticles was investigated. These microparticles were used as carrier for isoniazid. Among different
cross-linkers, glutaraldehyde was found to be the most effective cross-linker at the temperature and pH at which the reaction
was carried out. The loading efficiency and release behavior of loaded microparticles were found to be dependent on the amount
of cross-linker used, concentration of drug, and time of immersion. Maximum drug loading efficiency was observed at higher
immersion time. The release rate of isoniazid was more at higher pH compared to that of at lower pH. The sizes of the microparticles
were investigated by scanning electron microscope. In all the cases, the microparticles formed were found spherical in shape
except to those at low stirring speed where they were agglomerated. Fourier transform infrared study indicated the successful
incorporation of isoniazid into the microparticles. Differential scanning calorimetry study showed a molecular level dispersion
of isoniazid in the microparticles. X-ray diffraction study revealed the development of some crystallinity due to the encapsulation
of isoniazid. 相似文献
156.
Free radicals mediated oxidative stress has been implicated in the pathogenesis of smoking-related diseases and antioxidant nutrients are reported to prevent the oxidative damage induced by smoking. Therefore, the present study was conducted to evaluate the antioxidant role of bacoside A (triterpenoid saponin isolated from Bacopa monniera) against chronic cigarette smoking induced oxidative damage in rat brain. Adult male albino rats were exposed to cigarette smoke for a period of 12 weeks and simultaneously administered with bacoside A (10 mg/kg b.w./day, p.o.). Antioxidant status of the brain was assessed from the levels of reduced glutathione, vitamin C, vitamin E, and vitamin A and the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. The levels of copper, iron, zinc and selenium in brain and serum ceruloplasmin activity were also measured. Oxidative stress was evident from the diminished levels of both enzymatic and non-enzymatic antioxidants. Alterations in the levels of trace elements with accumulation of copper and iron, and depletion of zinc and selenium were also observed. Bacoside A administration improved the antioxidant status and maintained the levels of trace elements. These results suggest that chronic cigarette smoke exposure enhances oxidative stress, thereby disturbing the tissue defense system and bacoside A protects the brain from the oxidative damage through its antioxidant potential. 相似文献
157.
Maria G. Guzman Thomas Jaenisch Roger Gaczkowski Vo Thi Ty Hang Shamala Devi Sekaran Axel Kroeger Susana Vazquez Didye Ruiz Eric Martinez Juan C. Mercado Angel Balmaseda Eva Harris Efren Dimano Prisca Susan A. Leano Sutee Yoksan Elci Villegas Herminia Benduzu Iris Villalobos Jeremy Farrar Cameron P. Simmons 《PLoS neglected tropical diseases》2010,4(8)
Background
Early diagnosis of dengue can assist patient triage and management and prevent unnecessary treatments and interventions. Commercially available assays that detect the dengue virus protein NS1 in the plasma/serum of patients offers the possibility of early and rapid diagnosis.Methodology/Principal Findings
The sensitivity and specificity of the Pan-E Dengue Early ELISA and the Platelia™ Dengue NS1 Ag assays were compared against a reference diagnosis in 1385 patients in 6 countries in Asia and the Americas. Platelia was more sensitive (66%) than Pan-E (52%) in confirmed dengue cases. Sensitivity varied by geographic region, with both assays generally being more sensitive in patients from SE Asia than the Americas. Both kits were more sensitive for specimens collected within the first few days of illness onset relative to later time points. Pan-E and Platelia were both 100% specific in febrile patients without evidence of acute dengue. In patients with other confirmed diagnoses and healthy blood donors, Platelia was more specific (100%) than Pan-E (90%). For Platelia, when either the NS1 test or the IgM test on the acute sample was positive, the sensitivity versus the reference result was 82% in samples collected in the first four days of fever. NS1 sensitivity was not associated to disease severity (DF or DHF) in the Platelia test, whereas a trend for higher sensitivity in DHF cases was seen in the Pan-E test (however combined with lower overall sensitivity).Conclusions/Significance
Collectively, this multi-country study suggests that the best performing NS1 assay (Platelia) had moderate sensitivity (median 64%, range 34–76%) and high specificity (100%) for the diagnosis of dengue. The poor sensitivity of the evaluated assays in some geographical regions suggests further assessments are needed. The combination of NS1 and IgM detection in samples collected in the first few days of fever increased the overall dengue diagnostic sensitivity. 相似文献158.
159.
Drosophila body wall muscles are multinucleated syncytia formed by successive fusions between a founder myoblast and several fusion competent myoblasts. Initial fusion gives rise to a bi/trinucleate precursor followed by more fusion cycles forming a mature muscle. This process requires the functions of various molecules including the transmembrane myoblast attractants Dumbfounded (Duf) and its paralogue Roughest (Rst), a scaffold protein Rolling pebbles (Rols) and a guanine nucleotide exchange factor Loner. Fusion completely fails in a duf, rst mutant, and is blocked at the bi/trinucleate stage in rols and loner single mutants. We analysed the transmembrane and intracellular domains of Duf, by mutating conserved putative signaling sites and serially deleting the intracellular domain. These were tested for their ability to translocate and interact with Rols and Loner and to rescue the fusion defect in duf, rst mutant embryos. Studying combinations of double mutants, further tested the function of Rols, Loner and other fusion molecules. Here we show that serial truncations of the Duf intracellular domain successively compromise its function to translocate and interact with Rols and Loner in addition to affecting myoblast fusion efficiency in embryos. Putative phosphorylation sites function additively while the extreme C terminus including a PDZ binding domain is dispensable for its function. We also show that fusion is completely blocked in a rols, loner double mutant and is compromised in other double mutants. These results suggest an additive function of the intracellular domain of Duf and an early function of Rols and Loner which is independent of Duf. 相似文献
160.
Irom?Harimala?Chanu Laishram?Ronibala?Devi Nonibala?Khumanthem N.?Irabanta?Singh Dalip?Kumar Okram?Mukherjee?SinghEmail author 《Russian Journal of Bioorganic Chemistry》2017,43(2):177-185
Knoevenagel cyclocondensations of α-hydroxy naphthaldehyde with β-oxodithioesters and ketene dithioacetals yielded 2H-benzo[f]chromene-2-thiones and 2H-benzo[f]chromen-2-ones, respectively, in high yields. The newly synthesized compounds were evaluated for antifungal and antibacterial activities. Among them, compounds (2-furyl)(3-thioxo-3H-benzo[f]chromen-2-yl)methanone and phenyl(3-oxo-3H-benzo[f]chromen-2-yl)methanone exhibited excellent antifungal activity against tested fungi Curvularia lunata and Fusarium moniliforme. The highest antibacterial activity against the tested bacteria Escherichia coli and Staphylococcus aureus was observed for (4-chlorophenyl)(3-oxo-3H-benzo[f]chromen-2-yl)methanone. The results of antimicrobial screening demonstrate that (2-furyl)(3-thioxo-3H-benzo[f]chromen-2-yl)methanone, phenyl(3-oxo-3H-benzo[f]chromen-2-yl)methanone, and (4-chlorophenyl)(3-oxo-3H-benzo[f]chromen-2-yl)methanone are promising as antimicrobial drugs. 相似文献