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81.
R. Nath F. DeGuia J. Akbar S. A. Borosky† K. K. W. Wang 《Journal of neurochemistry》2001,81(S1):92-92
Neurotrophins support neuronal survival and axonal regeneration after injury. To test whether local expression of Neurotrophin-3 (NT-3) would elicit axonal regeneration we lesioned the corticospinal tract (CST) at the level of the hindbrain and measured the number of axons that would grow from the unlesioned CST to the contralateral side where NT-3 was over expressed at the lumbar level of the spinal cord. An adenoviral vector that carried the rat NT-3 gene and the NGF signal peptide driven by the EF1α promoter (Adv.EF-NT-3) was used. This model enabled us to test the effects of NT-3 on axonal regeneration without confounding injury processes. Biotinylated dextran amine (BDA) was injected into the rat cortex on unlesioned side to mark CST axons 10 days postlesion. Adenoviral vectors (1 × 109 pfu, Adv.EF-NT-3 or Adv.EF-LacZ) were delivered to lumbar spinal cord by retrograde transport from the sciatic nerve 4 days later. Histological examination 3 weeks later revealed that more BDA-labelled axons had grown from the unlesioned CST to the denervated side at the lumbar level. Morphometric measurements showed that a significantly larger number of BDA-labelled CST axons ( p < 0.001) were present in the animals that were treated with Adv.EF-NT-3 than those treated with Adv.EF-LacZ. These data demonstrate that local expression of NT-3 will support axonal regeneration in the injured spinal cord without adverse effects and suggest that gene delivery of neurotrophins may be an effective strategy for nervous system repair after injury.
Acknowledgements: Funded by NIH Grant NS35280 and by Mission Connect of the TIRR Foundation. 相似文献
Acknowledgements: Funded by NIH Grant NS35280 and by Mission Connect of the TIRR Foundation. 相似文献
82.
83.
Robert L. Seymour Prashant V. Mishra M. Akbar Khan & Michael P. Spector 《Molecular microbiology》1996,20(3):497-505
The starvation-stress response (SSR) of Salmonella typhimurium encompasses the physiological changes that occur upon starvation for an essential nutrient, e.g. C-source. A subset of SSR genes, known as core SSR genes, are required for the long-term starvation survival of the bacteria. Four core SSR loci have been identified in S. typhimuriumrpoSstiAstiB, and stiC. Here we report that in S. typhimurium C-starvation induced a greater and more sustainable cross-resistance to oxidative challenge (15 mM hydrogen peroxide (H2O2) for 40 min) than either N- or P-starvation. Of the four core SSR loci, only rpoS and stiC mutants exhibited a defective C-starvation-inducible cross-resistance to H2O2 challenge. Interestingly, (unadapted) log-phase S. typhimurium rpoS and stiA mutants were very sensitive to oxidative challenge. Based on this, we determined if these core SSR loci were important for H2O2 resistance developed during a 60 min adaptive exposure to 60 μM H2O2 (adapted cells). Both unadapted and adapted rpoS and stiA mutants were hypersensitive to a H2O2 challenge. In addition, a stiB mutant exhibited normal adaptive resistance for the first 20 mins of H2O2 challenge but then rapidly lost viability, declining to a level of about 1.5% of the wild-type strain. The results of these experiments indicate that: (i) the rpoS and stiC loci are essential for the development of C-starvation-inducible cross-resistance to oxidative challenge, and (ii) the rpoSstiA, and, in a delayed effect, stiB loci are needed for H2O2-inducible adaptive resistance to oxidative challenge. Moreover, we found that both stiA and stiB are induced by a 60 μM H2O2 exposure, but only stiA was regulated (repressed) by (reduced form) OxyR. 相似文献
84.
Nanocrystalline mixed metal oxides (MMO) of various metal cations were synthesized and were used for coating a piece of copper wire as a new high sensitive solid phase micro extraction (SPME) fiber in extraction and determination of BTEX compounds from the headspace of aqueous samples prior to GC-FID analysis. Under optimum extraction conditions, the proposed fiber exhibited low detection limits, and quantification limits, good reproducibility, simple and fast preparation method, high fiber capacity and high thermal and mechanical durability. These are some of the most important advantages of the new fiber. The proposed fiber was used for human hemoglobin upon interaction with benzene. Binding isotherm, Scatchard and Klotz logarithmic plots were constructed using HS-SPME-GC data, accurately. The obtained binding isotherm analyzed using Hill method. The Hill parameters have been obtained by calculating saturation parameter from the ratio of measured chromatographic peak areas in the presence and absence of hemoglobin. In this interaction, Hill coefficient and Hill constant determined as (nH = 6.14 and log KH = 6.47) respectively. These results reveal the cooperativity of hemoglobin upon interaction with benzene. 相似文献
85.
Teymour Vahedpour Jatinder Kaur Salar Hemmati Maryam Hamzeh-Mivehroud Ali Akbar Alizadeh Frank Wuest Siavoush Dastmalchi 《化学与生物多样性》2021,18(3):e2000832
A new series of 1,3,5-trisubstituted 2-pyrazolines for the inhibition of cyclooxygenase-2 (COX-2) were synthesized. The designed structures include a COX-2 pharmacophore SO2CH3 at the para-position of the phenyl ring located at C-5 of a pyrazoline scaffold. The synthesized compounds were tested for in vitro COX-1/COX-2 inhibition and cell toxicity against human colorectal adenocarcinoma cell lines HT-29. The lead compound (4-chlorophenyl){5-[4-(methanesulfonyl)phenyl]-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl}methanone ( 16 ) showed significant COX-2 inhibition (IC50=0.05±0.01 μM), and antiproliferative activity (IC50=5.46±4.71 μM). Molecular docking studies showed that new pyrazoline-based compounds interact via multiple hydrophobic and hydrogen-bond interactions with key binding site residues of the COX-2 enzyme. 相似文献
86.
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87.
Masoud Doroodgar Mahdi Delavari Moein Doroodgar Ali Abbasi Ali Akbar Taherian Abbas Doroodgar 《The Korean journal of parasitology》2016,54(1):9-14
Tamoxifen is an antagonist of the estrogen receptor and currently used for the treatment of breast cancer. The current treatment of cutaneous leishmaniasis with pentavalent antimony compounds is not satisfactory. Therefore, in this study, due to its antileishmanial activity, effects of tamoxifen on the growth of promastigotes and amastigotes of Leishmania major Iranian strain were evaluated in vitro. Promastigotes and amastigotes were treated with different concentrations (1, 5, 10, 20, and 50 μg/ml) and time periods (24, 48, and 72 hr) of tamoxifen. After tamoxifen treatment, MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5 biphenyl tetrazolium bromide assay) was used to determine the percentage of live parasites and Graph Pad Prism software to calculate IC50. Flow cytometry was applied to investigate the induction of tamoxifen-induced apoptosis in promastigotes. The half maximal inhibitory concentration (IC50) of tamoxifen on promastigotes was 2.6 μg/ml after 24 hr treatment. Flow cytometry analysis showed that tamoxifen induced early and late apoptosis in Leishmania promastigotes. While after 48 hr in control group the apoptosis was 2.0%, the 50 µg/L concentration of tamoxifen increased it to 59.7%. Based on the in vitro antileishmanial effect, tamoxifen might be used for leishmaniasis treatment; however, further researches on in vivo effects of tamoxifen in animal models are needed. 相似文献
88.
A. S. Bains E. S. Boek P. V. Coveney S. J. Williams M. V. Akbar 《Molecular simulation》2013,39(2):101-145
Abstract It is well known that the sodium smectite class of clays swells macroscopically in contact with water, whereas under normal conditions the potassium form does not. In recent work using molecular simulation methods, we have provided a quantitative explanation both for the swelling behaviour of sodium smectite clays and the lack of swelling of potassium smectites [1]. In the present paper, we apply similar modelling methods to study the mechanism of inhibition of clay-swelling by a range of organic molecules. Experimentally, it is known that polyalkylene glycols (polyethers) of intermediate to high relative molecular mass are effective inhibitors of smectite clay swelling. We use a range of atomistic simulation techniques, including Monte Carlo and molecular dynamics, to investigate the interactions between a selection of these compounds, water, and a model smectite clay mineral. These interactions occur by means of organised intercalation of water and organic molecules within the galleries between individual clay layers. The atomic interaction potentials deployed in this work are not as highly optimised as those used in our clay-cation-water work [1]. Nevertheless, our simulations yield trends and results that are in qualitative and sometimes semi-quantitative agreement with experimental findings on similiar (but not identical) systems. The internal energy of adsorption of simple polyethers per unit mass on the model clay is not significantly different from that for water adsorption; our Monte Carlo studies indicate that entropy is the driving force for the sorption of the simpler organic molecules inside the clay layers: a single long chain polyethylene glycol can displace a large number of water molecules, each of whose translational entropy is greatly enhanced when outside the clay. Hydrophobically modified polyalkylene glycols also enjoy significant van der Waals interactions within the layers which they form within the clay galleries. In conjunction with experimental studies, our work furnishes valuable insights into the relative effectiveness of the compounds considered and reveals the generic features that high performance clay-swelling inhibitors should possess. For optimal inhibitory activity, these compounds should be reasonably long chain linear organic molecules with localised hydrophobic and hydrophilic regions along the chain. On intercalation of these molecules within the clay layers, the hydrophobic regions provide an effective seal against ingress of water, while the hydrophilic ones enhance the binding of the sodium cations to the clay surface, preventing their hydration and the ensuing clay swelling. 相似文献
89.
90.
Ye Yuan Benedetto DiCiaccio Ying Li Ahmed S. Elshikha Denis Titov Brian Brenner Lee Seifer Hope Pan Nurdina Karic Mohammad A. Akbar Yuanqing Lu Sihong Song Lei Zhou 《Aging cell》2018,17(1)
Inflammaging plays an important role in most age‐related diseases. However, the mechanism of inflammaging is largely unknown, and therapeutic control of inflammaging is challenging. Human alpha‐1 antitrypsin (hAAT) has immune‐regulatory, anti‐inflammatory, and cytoprotective properties as demonstrated in several disease models including type 1 diabetes, arthritis, lupus, osteoporosis, and stroke. To test the potential anti‐inflammaging effect of hAAT, we generated transgenic Drosophila lines expressing hAAT. Surprisingly, the lifespan of hAAT‐expressing lines was significantly longer than that of genetically matched controls. To understand the mechanism underlying the anti‐aging effect of hAAT, we monitored the expression of aging‐associated genes and found that aging‐induced expressions of Relish (NF‐?B orthologue) and Diptericin were significantly lower in hAAT lines than in control lines. RNA‐seq analysis revealed that innate immunity genes regulated by NF‐kB were significantly and specifically inhibited in hAAT transgenic Drosophila lines. To confirm this anti‐inflammaging effect in human cells, we treated X‐ray‐induced senescence cells with hAAT and showed that hAAT treatment significantly decreased the expression and maturation of IL‐6 and IL‐8, two major factors of senescence‐associated secretory phenotype. Consistent with results from Drosophila,RNA‐seq analysis also showed that hAAT treatment significantly inhibited inflammation related genes and pathways. Together, our results demonstrated that hAAT significantly inhibited inflammaging in both Drosophila and human cell models. As hAAT is a FDA‐approved drug with a confirmed safety profile, this novel therapeutic potential may make hAAT a promising candidate to combat aging and aging‐related diseases. 相似文献