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71.
Agonist stimulation of G protein-coupled receptors causes receptor activation, phosphorylation, beta-arrestin binding and receptor internalization. Angiotensin II (AngII) causes rapid internalization of the AT1 receptors, whereas AngII-bound AT2 receptors do not internalize. Although the activation of the rat AT1A receptor with AngII causes translocation of beta-arrestin2 to the receptor, no association of this molecule with the AT2 receptor can be detected after AngII treatment with confocal microscopy or bioluminescence resonance energy transfer. These data demonstrate that the two subtypes of angiotensin receptors have different mechanisms of regulation. 相似文献
72.
Production of Trichoderma strains with pesticide-polyresistance by mutagenesis and protoplast fusion 总被引:1,自引:0,他引:1
Hatvani L Manczinger L Kredics L Szekeres A Antal Z Vágvölgyi C 《Antonie van Leeuwenhoek》2006,89(3-4):387-393
The sensitivity of two cold-tolerant Trichoderma strains belonging to the species T. harzianum and T.␣atroviride was determined to a series of pesticides widely used in agriculture. From the 16 pesticides tested, seven fungicides: copper sulfate, carbendazim, mancozeb, tebuconazole, imazalil, captan and thiram inhibited colony growth of the test strains significantly with minimal inhibitory concentrations of 300, 0.4, 50, 100, 100, 100 and 50 g/ml, respectively. Mutants resistant to carbendazim and tebuconazole were produced from both wild type strains by means of UV-mutagenesis. The cross-resistance capabilities and in␣vitro antagonistic properties of the mutants were determined. Carbendazim-resistant mutants showed total cross-resistance to benomyl and thiabendazole at a concentration of 20 g/ml. Intraspecific protoplast fusion was carried out between carbendazim- and tebuconazole-resistant mutants of both parental strains, and putative haploid recombinants with stable resistance to both pesticides were produced in the case of T.␣atroviride. These pesticide-polyresistant progenies are potential candidates for application in an integrated pest management system.This work was presented as an oral lecture in section ‘Agriculture, Soil, Forest Microbiology’ at the BioMicroWorld2005 conference. 相似文献
73.
In autoimmune (type 1) diabetes, autoreactive lymphocytes destroy pancreatic β-cells responsible for insulin synthesis. To
assess the feasibility of gene therapy for type 1 diabetes, recombinant vaccinia virus (rVV) vectors were constructed expressing
pancreatic islet autoantigens proinsulin (INS) and a 55-kDa immunogenic peptide from glutamic acid decarboxylase (GAD), and
the immunomodulatory cytokine interleukin (IL)-10. To augment the beneficial effects of recombinant virus therapy, the INS
and GAD genes were fused to the C terminus of the cholera toxin B subunit (CTB). Five-week-old non-obese diabetic (NOD) mice
were injected once with rVV. Humoral antibody immune responses and hyperglycemia in the infected mice were analyzed.
Only 20% of the mice inoculated with rVV expressing the CTB::INS fusion protein developed hyperglycemia, in comparison to
70% of the mice in the uninoculated animal group. Islets from pancreatic tissues isolated from euglycemic mice from this animal
group showed no sign of inflammatory lymphocyte invasion. Inoculation with rVV producing CTB::GAD or IL-10 was somewhat less
effective in reducing diabetes. Humoral antibody isotypes of hyperglycemic and euglycemic mice from all treated groups possessed
similar IgG1/IgG2c antibody titer ratios from 19 to 32 wk after virus inoculation. In comparison with uninoculated mice, 11-wk-old
NOD mice injected with virus expressing CTB::INS were delayed in diabetes onset by more than 4 wk. The experimental results
demonstrate the feasibility of using rVV expressing CTB::INS fusion protein to generate significant protection and therapy
against type 1 diabetes onset and progression. 相似文献
74.
The airborne dispersal of the anamorphs of the Gibberella fujikuroi species complex was studied under pre- and postharvest maize (corn) production conditions using a 3-stage Andersen sampler.
The aim of this study was to identify and analyse the size distribution of such species in air samples. Differences were observed
between the concentration of large- and small-sized propagules (identified as aggregates and single microconidia, respectively),
but the difference was only significant during a high concentration period (October 2007, P = 0.009). No correlation was found between the concentration of fusaria found at different sampling heights (10 and 150 cm
above ground level). Fusarium isolates were collected and identified based on morphological characters and using species-specific PCR assays. The PCR analysis
confirmed morphological identification of F. verticillioides, F. proliferatum and F. subglutinans. High concentrations were found during the maize harvest, loading and corn shelling. Our results showed that the monitoring
of F. verticillioides should be performed at a single sampling height. 相似文献
75.
Mukhopadhyay P Horváth B Zsengellér Z Zielonka J Tanchian G Holovac E Kechrid M Patel V Stillman IE Parikh SM Joseph J Kalyanaraman B Pacher P 《Free radical biology & medicine》2012,52(2):497-506
Cisplatin is a widely used antineoplastic agent; however, its major limitation is the development of dose-dependent nephrotoxicity whose precise mechanisms are poorly understood. Here we show not only that mitochondrial dysfunction is a feature of cisplatin nephrotoxicity, but also that targeted delivery of superoxide dismutase mimetics to mitochondria largely prevents the renal effects of cisplatin. Cisplatin induced renal oxidative stress, deterioration of mitochondrial structure and function, an intense inflammatory response, histopathological injury, and renal dysfunction. A single systemic dose of mitochondrially targeted antioxidants, MitoQ or Mito-CP, dose-dependently prevented cisplatin-induced renal dysfunction. Mito-CP also prevented mitochondrial injury and dysfunction, renal inflammation, and tubular injury and apoptosis. Despite being broadly renoprotective against cisplatin, Mito-CP did not diminish cisplatin's antineoplastic effect in a human bladder cancer cell line. Our results highlight the central role of mitochondrially generated oxidants in the pathogenesis of cisplatin nephrotoxicity. Because similar compounds seem to be safe in humans, mitochondrially targeted antioxidants may represent a novel therapeutic approach against cisplatin nephrotoxicity. 相似文献
76.
Mukhopadhyay P Horváth B Zsengellėr Z Bátkai S Cao Z Kechrid M Holovac E Erdėlyi K Tanchian G Liaudet L Stillman IE Joseph J Kalyanaraman B Pacher P 《Free radical biology & medicine》2012,53(5):1123-1138
Mitochondrial reactive oxygen species generation has been implicated in the pathophysiology of ischemia-reperfusion (I/R) injury; however, its exact role and its spatial-temporal relationship with inflammation are elusive. Herein we explore the spatial-temporal relationship of oxidative/nitrative stress and inflammatory response during the course of hepatic I/R and the possible therapeutic potential of mitochondrial-targeted antioxidants, using a mouse model of segmental hepatic ischemia-reperfusion injury. Hepatic I/R was characterized by early (at 2h of reperfusion) mitochondrial injury, decreased complex I activity, increased oxidant generation in the liver or liver mitochondria, and profound hepatocellular injury/dysfunction with acute proinflammatory response (TNF-α, MIP-1α/CCL3, MIP-2/CXCL2) without inflammatory cell infiltration, followed by marked neutrophil infiltration and a more pronounced secondary wave of oxidative/nitrative stress in the liver (starting from 6h of reperfusion and peaking at 24h). Mitochondrially targeted antioxidants, MitoQ or Mito-CP, dose-dependently attenuated I/R-induced liver dysfunction, the early and delayed oxidative and nitrative stress response (HNE/carbonyl adducts, malondialdehyde, 8-OHdG, and 3-nitrotyrosine formation), and mitochondrial and histopathological injury/dysfunction, as well as delayed inflammatory cell infiltration and cell death. Mitochondrially generated oxidants play a central role in triggering the deleterious cascade of events associated with hepatic I/R, which may be targeted by novel antioxidants for therapeutic advantage. 相似文献
77.
78.
M Szekeres GL Nádasy G Turu E Soltész-Katona ZE Tóth A Balla KJ Catt L Hunyady 《The Journal of biological chemistry》2012,287(37):31540-31550
In the vascular system angiotensin II (Ang II) causes vasoconstriction via the activation of type 1 angiotensin receptors. Earlier reports have shown that in cellular expression systems diacylglycerol produced during type 1 angiotensin receptor signaling can be converted to 2-arachidonoylglycerol, an important endocannabinoid. Because activation of CB(1) cannabinoid receptors (CB(1)R) induces vasodilation and reduces blood pressure, we have tested the hypothesis that Ang II-induced 2-arachidonoylglycerol release can modulate its vasoconstrictor action in vascular tissue. Rat and mouse skeletal muscle arterioles and mouse saphenous arteries were isolated, pressurized, and subjected to microangiometry. Vascular expression of CB(1)R was demonstrated using Western blot and RT-PCR. In accordance with the functional relevance of these receptors WIN55212, a CB(1)R agonist, caused vasodilation, which was absent in CB(1)R knock-out mice. Inhibition of CB(1)Rs using O2050, a neutral antagonist, enhanced the vasoconstrictor effect of Ang II in wild type but not in CB(1)R knock-out mice. Inverse agonists of CB(1)R (SR141716 and AM251) and inhibition of diacylglycerol lipase using tetrahydrolipstatin also augmented the Ang II-induced vasoconstriction, suggesting that endocannabinoid release modulates this process via CB(1)R activation. This effect was independent of nitric-oxide synthase activity and endothelial function. These data demonstrate that Ang II stimulates vascular endocannabinoid formation, which attenuates its vasoconstrictor effect, suggesting that endocannabinoid release from the vascular wall and CB(1)R activation reduces the vasoconstrictor and hypertensive effects of Ang II. 相似文献
79.
Hegyi M Félné Semsei A Jakab Z Antal I Kiss J Szendrõi M Csóka M Kovács G 《Magyar onkologia》2012,56(1):30-37
The objective of this report was to estimate long-term outcome and prognostic factors in children and adolescents with osteosarcoma. To evaluate the efficacy of surgery and multiagent chemotherapy for treating osteosarcoma, we reviewed 122 cases (65 males, 57 females, mean age 13.8 ± 3.6 years) treated at the Second Department of Pediatrics in Budapest between 1988 and 2006. Demographic parameters, tumor-related and treatment-related variables, response, overall survival (OS) and event-free survival (EFS) were analyzed. The 5-year OS and EFS were 68% and 61.5%, respectively. OS of patients without metastasis was 79%, while OS with early metastasis was 17%. Survival of patients with amputation (n=30) was not significantly different from that of patients with limb-salvage surgery (n=82), but all patients without radical surgery died. Gender and histological classification had no prognostic significance. Patients with localized tumors in extremities had increased survival compared to those with axial skeleton tumors (p=0.013). Poor histological response to neoadjuvant chemotherapy (rate of survivor tumor cells >10%) was associated with decreased survival (p=0.018). Patients under 14 years had better EFS than patients over 14 years (p=0.008). Our results demonstrate that younger patients with localized osteosarcoma of the extremities who receive limb-salvage surgery and chemotherapy have an excellent survival. 相似文献
80.
Swenson MS Anderson J Ash A Gaurav P Sukosd Z Bader DA Harvey SC Heitsch CE 《BMC research notes》2012,5(1):341
ABSTRACT: BACKGROUND: Accurate and efficient RNA secondary structure prediction remains an important open problem in computational molecular biology. Historically, advances in computing technology have enabled faster and more accurate RNA secondary structure predictions. Previous parallelized prediction programs achieved significant improvements in runtime, but their implementations were not portable from niche high-performance computers or easily accessible to most RNA researchers. With the increasing prevalence of multi-core desktop machines, a new parallel prediction program is needed to take full advantage of today's computing technology. FINDINGS: We present here the first implementation of RNA secondary structure prediction by thermodynamic optimization for modern multi-core computers. We show that GTfold predicts secondary structure in less time than UNAfold and RNAfold, without sacrificing accuracy, on machines with four or more cores. CONCLUSIONS: GTfold supports advances in RNA structural biology by reducing the timescales for secondary structure prediction. The difference will be particularly valuable to researchers working with lengthy RNA sequences, such as RNA viral genomes. 相似文献