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61.
The present study aimed to formulate orodispersible tablets of flutamide (FTM) to increase its bioavailability. Orodispersible tablets were prepared by direct compression technique using three different approaches namely; super-disintegration, effervescence and sublimation. Different combined approaches were proposed and evaluated to optimize tablet characteristics. Sodium starch glycolate (SSG) was used as the superdisintegrant. The prepared powder mixtures were subjected to both pre and post compression evaluation parameters including; IR spectroscopy, micromeritics properties, tablet hardness, friability, wetting time, disintegration time and in-vitro drug release. IR studies indicated that there was no interaction between the drug and the excipients used except Ludipress. The results of micromeritics studies revealed that all formulations were of acceptable to good flowability. Tablet hardness and friability indicated good mechanical strength. Wetting and dispersion times decreased from 46 to 38 s by increasing the SSG concentration from 3.33 to 6.66% w/w in tablets prepared by superdisintegration method. The F8 formulation which was prepared by combined approaches of effervescence and superdisintegrant addition gave promising results for tablet disintegration and wetting times but failed to give faster dissolution rate. The incorporation of 1:5 solid dispersion of FTM: PEG 6000 instead of the pure drug in the same formulation increased the drug release rate from 73.12 to 96.99% after 15 min. This increase in the dissolution rate may be due to the amorphization of the drug during the solid dispersion preparation. The presence of the amorphous form of the drug was shown in the IR spectra. 相似文献
62.
Maha Sherif Hüseyin Demirbilek Atilla ayr Sophia Tahir Büra avdarl Meliha Demiral Aye Nurcan Cebeci Dou Vurall Sofia Asim Rahman Edip Unal Gnül Büyükylmaz Riza Taner Baran Mehmet Nuri
zbek Khalid Hussain 《Journal of clinical research in pediatric endocrinology》2021,13(1):34
Objective:Bi-allelic mutations in the wolframin gene (WFS1) cause Wolfram syndrome 1 (WS1 or DIDMOAD) characterized by non-autoimmune diabetes mellitus, optic atrophy, diabetes insipidus, sensorineural deafness, urinary tract abnormalities, and neuropsychiatric disorders. Patients presenting with an incomplete phenotype of WS1 were evaluated using homozygosity mapping and subsequent whole-exome sequencing.Methods:Four unrelated consanguineous Turkish families, including seven affected children, and their unaffected parents and siblings were evaluated. Homozygosity mapping was performed, followed by whole-exome sequencing of WFS1. Mutations were classified according to results of “in silico” analyses, protein prediction, and functional consequences.Results:Homozygosity mapping confirmed shared homozygous regions on chromosome 4 (chr4p16.1) between the affected individuals, that was absent in their unaffected siblings. Exome sequencing identified three novel (c.1215T>A, c.554G>A, c.1525_1540dup) and one known (c.1522_1523delTA) mutations in WFS1. All mutations were predicted to cause stop codon leading to early termination of protein synthesis and complete loss-of-function. All patients were found to be homozygous for the change, with parents and other unaffected siblings being carriers.Conclusion:Our study expands the mutation spectrum of WSF1 mutations with three novel mutations. Homozygosity mapping may provide enrichment for molecular genetic analysis and early diagnosis of WS1 patients with incomplete phenotype, particularly in consanguineous pedigrees. 相似文献
63.
Hugues Lucron Alban-Elouen Baruteau Caroline Ovaert Ali Houeijeh Mélanie Brard Patrice Guerin François Bourlon Claire Dauphin Saskia Tuttle Maha Tagorti Rishika Banydeen François Godart 《Congenital heart disease》2022,17(4):421-436
Objectives: We aim to describe the efficacy, safety, and characteristics of the Amplatzer Vascular Plug (AVP) II and IV “off-label” use for multiple cardiovascular occlusions in children under 10 years. Methods: Observational retrospective multicenter (2007–2020, 6 centers) review of paediatric procedures using AVP II or IV. Results: A total of 125 children (49.6% aged ≤ 1 year, 147 lesions) underwent 136 successive procedures (success rate: 98.5%) using 169 devices (109 AVP IV, 60 AVP II). The mean device diameter was 7.7 ± 3.2 mm (4–20 mm). The median AVP size to vessel diameter ratio was 1.3 (0–2). The median age and weight at implantation were 1.0 year (0.01–9.98) and 8.4 kg (1–69). Procedures were heterogeneous (55 patent ductus arteriosus (PDA), 28 collaterals, 18 sequestrations, 22 arteriovenous/veinovenous/coronary fistulas, 6 vertical veins, 6 conduits, 5 ventricular septal defects, 7 miscellaneous). Day 1 and 6-month occlusion rates were respectively 94.8% and 98.5%. Major adverse events (MAE) occurred in 5.2% of cases (no procedure-related deaths), and more frequently in weight ≤ 5 kg (p = 0.01), younger patients (p = 0.03) during PDA closure (p = 0.02) of tubular types (p = 0.02) using larger devices (p = 0.03) and AVP II (p = 0.003). Independent predictor of MAE risk was a higher AVP diameter to patient weight ratio (Odds-ratio: 2.33, 95% confidence interval 1.31–4.13, p = 0.004, optimal cut off: 1.45). Conclusions: Both AVPs are safe and effective for percutaneous occlusions in children under 10. Such devices represent an alternative “off label” use for well selected paediatric patients. 相似文献
64.
65.
CpG-A and CpG-B oligonucleotides differentially enhance human peptide-specific primary and memory CD8+ T-cell responses in vitro 总被引:1,自引:0,他引:1
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Rothenfusser S Hornung V Ayyoub M Britsch S Towarowski A Krug A Sarris A Lubenow N Speiser D Endres S Hartmann G 《Blood》2004,103(6):2162-2169
Two distinct types of CpG oligodeoxynucleotide (ODN) have been identified that differ in their capacity to stimulate antigen-presenting cells: CpG-A induces high amounts of interferon-alpha (IFN-alpha) and IFN-beta in plasmacytoid dendritic cells (PDCs), whereas CpG-B induces PDC maturation and is a potent activator of B cells but stimulates only small amounts of IFN-alpha and IFN-beta. Here we examined the ability of these CpG ODNs to enhance peptide-specific CD8+ T-cell responses in human peripheral blood mononuclear cells (PBMCs). The frequency of influenza matrix-specific "memory" CD8+ T cells was increased by both types of CpG ODN, whereas the frequency of Melan-A specific "naive" CD8+ T cells increased on stimulation with CpG-B but not with CpG-A. The presence of PDCs in PBMCs was required for this CpG ODN-mediated effect. The expanded cells were cytotoxic and produced IFN- on peptide restimulation. Soluble factors induced by CpG-A but not CpG-B increased the granzyme-B content and cytotoxicity of established CD8+ T-cell clones, each of which was IFN-alpha/-beta dependent. In conclusion, CpG-B seems to be superior for priming CD8+ T-cell responses, and CpG-A selectively enhances memory CD8+ T-cell responses and induces cytotoxicity. These results demonstrate distinct functional properties of CpG-A and CpG-B with regard to CD8 T cells. 相似文献
66.
Transplant candidates might manifest circulating antibodies against human leukocyte antigens and nonhuman leukocyte antigens, a condition termed allosensitization. The presence of these antibodies decreases a given candidate's possible donor pool, thereby prolonging the time to transplantation. They are also associated with poorer posttransplant outcomes including increased morbidity and mortality. With the increasing use of ventricular assist devices as a bridge to transplantation, the prevalence of allosensitized transplant candidates has increased. This has implications for transplant programs in terms of donor-recipient matching and managing transplant-related complications, which are more common in this high risk cohort. Controversy exists as to the best approach in managing sensitized patients, before and after transplantation. Transplant centres have used various strategies to reduce antibody loads with mixed results being reported; moreover, it remains unclear as to whether attempts at desensitization translate into better posttransplant outcomes. As an alternative management approach, some centres participate in large organ sharing strategies and allocate organs based on the probability of finding a successful donor-recipient match. In this article, the immunological basis of allosensitization, its causes, implications, and therapeutic strategies to manage sensitized patients are reviewed. The literature in relation to desensitization therapies in heart transplant candidates is also reviewed. 相似文献
67.
Maha Hoteit Asma Arabi Robert Habib Rami Mahfouz Rafic Baddoura Georges Halaby Ghada El-Hajj Fuleihan 《Metabolism: clinical and experimental》2014
Objective
Variants of estrogen receptor α (ERα) have been associated with obesity, dyslipidemia, diabetes and blood pressure. The Middle East registers some of the highest rate of metabolic syndrome worldwide. The aim of this study is to investigate the relationship between metabolic syndrome, a clustered combination of these metabolic factors, and polymorphisms PvuII and XbaI of ERα in Lebanese Caucasian elderly overweight subjects.Material/Methods
250 Caucasian Lebanese unrelated elderly men and women, median age 71 years, were studied. ERα intronic polymorphisms variants, PvuII and XbaI diplotypes and genotypes, were examined. Associations with metabolic syndrome, defined by the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI), and its components, namely high density lipoprotein (HDL), fasting glucose levels, blood pressure, and waist circumference were evaluated in regression models.Results
ER α diplotypes and genotypes distributions were similar between participants with and without metabolic syndrome, in the overall group of subjects, and by gender. No consistent associations between the diplotypes and genotypes tested and metabolic syndrome, or its components, could be detected.Conclusions
Genetic variants in ERα were not associated with metabolic syndrome or its components, in a group of 250 Lebanese Caucasian elderly participants, a group with a high prevalence of metabolic syndrome. 相似文献68.
Maha F. Elbaloula Runqiang Yang Qianghui Guo 《International journal of food sciences and nutrition》2014,65(1):48-52
Germination is of importance to improving nutritional attributes of cereal grains for human consumption. The effect of germination time on major nutrient compositions and functional properties of sorghum flour was investigated in this study. Grains of Butanua, a new Sudanese sorghum cultivar, were germinated for 0,?1,?2, and 3 days to analyze their chemical and functional properties. The contents of starch, protein, oil, foaming stability, bulk density, and least gelation concentration of sorghum flour decreased, whereas oil absorption capacity, foaming capacity, and emulsion capacity and stability enhanced with an increase in germination time. Improved functional properties of sorghum flour by germination of the grains not only make it useful and suitable for various food processing formulations, but also improve the food product quality. This new finding will beneficially help develop innovative technologies, design new types of functional foods, and promote both sorghum production and relevant food processing industry in the future. 相似文献
69.
Sandra Donkervoort Payam Mohassel Lucia Laugwitz Maha S. Zaki Erik‐Jan Kamsteeg Reza Maroofian Katherine R. Chao Corien C. Verschuuren‐Bemelmans Veronka Horber Annemarie J. M. Fock Riley M. McCarty Minal S. Jain Victoria Biancavilla Grace McMacken Matthew Nalls Nicol C. Voermans Hasnaa M. Elbendary Molly Snyder Chunyu Cai Tanya J. Lehky Valentina Stanley Susan T. Iannaccone A. Reghan Foley Hanns Lochmüller Joseph Gleeson Henry Houlden Tobias B. Haack Rita Horvath Carsten G. Bönnemann 《American journal of medical genetics. Part A》2020,182(10):2272-2283
Synaptotagmins are integral synaptic vesicle membrane proteins that function as calcium sensors and regulate neurotransmitter release at the presynaptic nerve terminal. Synaptotagmin‐2 (SYT2), is the major isoform expressed at the neuromuscular junction. Recently, dominant missense variants in SYT2 have been reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment. These variants are thought to have a dominant‐negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated. Here we report seven patients of five families, with biallelic loss of function variants in SYT2, clinically manifesting with a remarkably consistent phenotype of severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings were consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in three patients showed clinical improvement with increased strength and function. This series further establishes SYT2 as a CMS‐disease gene and expands its clinical and genetic spectrum to include recessive loss‐of‐function variants, manifesting as a severe congenital onset presynaptic CMS with potential treatment implications. 相似文献
70.
Paschalis Vergidis Raymund R. Razonable L. Joseph Wheat Lynn Estes Angela M. Caliendo Lindsey R. Baden John R. Wingard John Baddley Maha Assi Steven Norris Pranatharthi Chandrasekar Ryan Shields Hong Nguyen Alison Freifeld Richard Kohler Martin Kleiman Thomas J. Walsh Chadi A. Hage 《Journal of clinical microbiology》2014,52(6):2199-2201
Piperacillin-tazobactam (PTZ) is known to cause false-positive results in the Platelia Aspergillus enzyme-linked immunoassay (EIA), due to contamination with galactomannan (GM). We tested 32 lots of PTZ and 27 serum specimens from patients receiving PTZ. GM was not detected in the lots of PTZ; one serum specimen (3.7%) was positive. PTZ formulations commonly used in the United States today appear to be a rare cause for false-positive GM results. 相似文献