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11.
Wilson's disease in children: 37-year experience and revised King's score for liver transplantation.
Anil Dhawan Rachel M Taylor Paul Cheeseman Pamela De Silva Leah Katsiyiannakis Giorgina Mieli-Vergani 《Liver transplantation》2005,11(4):441-448
Wilson's disease (WD) is a rare liver-based disorder of copper metabolism. Prognostic criteria described by our group in 1986 to predict death without transplantation have not been universally validated. The clinical features of 88 children were reviewed, retrospectively in 74 and prospectively in 14. Data from the retrospectively recruited patients that died or survived on long-term chelation were used to evaluate the validity of our old scoring system and to devise a new prognostic index, then assessed in the 14 prospectively recruited patients. Using the old scoring system, 5 children scoring > or = 7, the cutoff value for death without transplantation, survived, whereas 4 scoring < or = 7 died (sensitivity 87% and specificity 90%). A new index based on serum bilirubin, international normalized ratio, aspartate aminotransferase (AST), and white cell count (WCC) at presentation identified a cutoff score of 11 for death and proved to be 93% sensitive and 98% specific, with a positive predictive value of 88%. When the new index was evaluated prospectively in 14 patients, it predicted the need for transplantation in only the 4 who required it, although 1 child with a score of 11 survived on medical treatment. In conclusion, the new Wilson Index is more sensitive and specific in predicting mortality without transplantation than the old scoring system, but needs to be validated in a larger number of patients. 相似文献
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Surojit Paul Peter Olausson Deepa V Venkitaramani Irina Ruchkina Timothy D Moran Natalie Tronson Evan Mills Shawn Hakim Michael W Salter Jane R Taylor Paul J Lombroso 《Neuropsychopharmacology》2007,61(9):1049-1061
BACKGROUND: Formation of long-term memories is critically dependent on extracellular-regulated kinase (ERK) signaling. Activation of the ERK pathway by the sequential recruitment of mitogen-activated protein kinases is well understood. In contrast, the proteins that inactivate this pathway are not as well characterized. METHODS: Here we tested the hypothesis that the brain-specific striatal-enriched protein tyrosine phosphatase (STEP) plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation. RESULTS: STEP co-localizes with the ERKs within neurons of the lateral amygdala. A substrate-trapping STEP protein binds to the ERKs and prevents their nuclear translocation after glutamate stimulation in primary cell cultures. Administration of TAT-STEP into the lateral amygdala (LA) disrupts long-term potentiation (LTP) and selectively disrupts fear memory consolidation. Fear conditioning induces a biphasic activation of ERK1/2 in the LA with an initial activation within 5 minutes of training, a return to baseline levels by 15 minutes, and an increase again at 1 hour. In addition, fear conditioning results in the de novo translation of STEP. Inhibitors of ERK1/2 activation or of protein translation block the synthesis of STEP within the LA after fear conditioning. CONCLUSIONS: Together, these data imply a role for STEP in experience-dependent plasticity and suggest that STEP modulates the activation of ERK1/2 during amygdala-dependent memory formation. The regulation of emotional memory by modulating STEP activity may represent a target for the treatment of psychiatric disorders such as posttraumatic stress disorder (PTSD), panic, and anxiety disorders. 相似文献
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C Sundaram Deepa Goel Shantveer G Uppin S Seethajayalakshmi Rupam Borgohain 《Journal of clinical neuroscience》2007,14(9):882-886
BACKGROUND: Intracranial true mycotic aneurysms are uncommon and usually fatal. We report two patients with basilar mycotic aneurysms due to Aspergillus species following surgical interventions. Both patients had subarachnoid hemorrhage and diagnosis was made at autopsy only. The literature regarding etiology, clinical presentation, predisposing conditions and outcome of intracranial true mycotic aneurysms is reviewed from 1990-2005. A high index of clinical suspicion with prompt diagnosis and early treatment may improve patient outcome. 相似文献
16.
Preventive and therapeutic role of vitamin E in chronic plumbism 总被引:1,自引:0,他引:1
The ability of vitamin E to prevent or treat experimental lead intoxication was investigated in rats. Lead ingestion (10 mg/kg, lead as lead acetate, orally for 6 weeks) significantly inhibited the activity of blood delta-aminolevulinic acid dehydratase (ALAD), reduced the brain dopamine (DA) contents, enhanced the blood zinc protoporphyrin, and enhanced the urinary excretion of delta-aminolevulinic acid (ALA). Lead exposure also elevated brain norepinephrine, homovanillic acid, and 5-hydroxyindole acetic acid (5-HIAA) levels and concentration of lead in blood and tissue. Simultaneous supplementation of vitamin E along with lead significantly reduced the inhibition of blood ALAD activity, brain DA and 5-HIAA levels, and elevation of urinary ALA excretion. Blood and liver lead concentrations were also significantly reduced by simultaneous supplementation with vitamin E. Postlead exposure treatment with vitamin E was ineffective in reducing the lead-induced effects, except that the inhibition of blood ALAD activity was slightly reduced. The present results suggest that vitamin E given simultaneously with lead is effective in reducing the severity of lead intoxication. 相似文献
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R Dhawan U C Chaturvedi M Khanna A Mathur B L Tekwani V C Pandey R N Rai 《International journal of experimental pathology》1991,72(1):31-39
The role of calcium ions (Ca2+) in the cytotoxic activity of the dengue type 2 virus (DV)-induced macrophage (M phi) cytotoxin (CF2) was investigated in the present study. The findings show that CF2 prepared in Ca(2+)-free medium had no cytotoxic activity on normal mouse spleen cells suspended in Ca(2+)-free medium but killed the cells suspended in the medium with Ca2+. Substitution with calcium chloride restored the cytotoxic activity of CF2 the optimal dose being 10(-4) M concentration. CF2 induced an influx of Ca2+, as assayed by uptake of radiolabelled calcium chloride (45Ca), in the susceptible target cells, viz. M phi and T lymphocytes. The cytotoxic activity of CF2 as well as the CF2-induced influx of 45Ca was inhibited by treatment of the target cell with the calcium channel blocking drugs verapamil and nifedipine. Thus, the presence of Ca2+ is obligatory for the cytotoxic activity of CF2 and cell death is associated with increased intracellular Ca2+. 相似文献
19.
Tetracycline-regulated gene expression following direct gene transfer into mouse skeletal muscle 总被引:7,自引:0,他引:7
Jyotsna Dhawan Thomas A. Rando Sarah L. Elson Hermann Bujard Helen M. Blau 《Somatic Cell and Molecular Genetics》1995,21(4):233-240
For most experimental and therapeutic applications of gene transfer, regulation of the timing and level of gene expression is preferable to constitutive gene expression. Among the systems that have been developed for pharmacologically controlled gene expression in mammalian cells, the bacterial tetracycline (tet)-responsive system has the advantage that it is dependent on a drug (tet) that is both highly specific and non-toxic. The tet-responsive system has been previously used to modulate expression of cell cycle regulatory proteins in cultured cells, reporter genes in plants and transgenic mice and reporter genes directly injected into the heart. Here we show that orally or parenterally administered tet regulates expression of tet-responsive plasmids injected directly into mouse skeletal muscle. Reporter gene expression was suppressed by two orders of magnitude in the presence of tet, and that suppression was reversed when tet was withdrawn. These data show that skeletal muscle offers an accessible and well characterized target tissue for tet-controlled expression of genesin vivo, suggesting applications to developmental studies and gene therapy. 相似文献
20.
Lack of IgG4 antibody response to carbohydrate antigens in patients with lymphatic filariasis. 总被引:4,自引:0,他引:4
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It has been suggested that humans are genetically restricted from making IgG4 antibody responses to carbohydrate antigens. To test this hypothesis we examined sera from 35 patients with bancroftian filariasis (an infection known to induce very high levels of IgG4 antibodies to the parasite and known to be associated with repeated streptococcal infections) as well as from 15 normal individuals for their IgG and IgG subclass responses to streptococcal protein [streptolysin-O (SO), deoxyribonuclease B (DB)] and carbohydrate [group A carbohydrate (GAC)] antigens. Levels of IgG antibodies to all three antigens were found to be significantly higher in the filariasis patients compared to normals (P less than 0.01), and the subclass composition of these antibodies proved heterogenous. Although responses to all three antigens included IgG1, IgG2 and IgG3 antibodies and although IgG4 responses to the proteins SO and DB were significantly higher in the filariasis patients than in normals (P less than 0.001), more importantly there were no detectable anti-GAC IgG4 antibodies in either study group. These observations, coupled with our earlier finding of the absence of IgG4 responses to phosphocholine (PC) in patients with lymphatic filariasis, suggest that even the chronic antigenic stimulation of filarial helminth infection, which leads to very prominent IgG4 responses to protein antigens, cannot overcome the genetic restriction in humans for making IgG4 antibodies to carbohydrate antigens, whether of parasite or non-parasite origin. 相似文献