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91.
Peroxisome proliferator-activated receptor gamma is expressed in airways and inhibits features of airway remodeling in a mouse asthma model 总被引:10,自引:0,他引:10
Honda K Marquillies P Capron M Dombrowicz D 《The Journal of allergy and clinical immunology》2004,113(5):882-888
BACKGROUND: Allergic asthma is associated with persistent functional and structural changes in the airways and involves many different cell types. Peroxisome proliferator-activated receptor gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily, is predominantly expressed in adipose tissue and plays a major role in regulating adipocyte differentiation and glucose metabolism. Recently, PPAR-gamma has been shown to play an important role in the control of inflammatory responses, including within the lung, acting on both immune and nonimmune cells. OBJECTIVE: Our aim was to assess the anti-inflammatory potential of a PPAR-gamma agonist locally delivered by means of nebulization. METHODS: We used a mouse model of asthma induced by sensitization and airway challenge with ovalbumin. Ciglitazone, a PPAR-gamma agonist, was administered by means of nebulization alone at the time of antigen challenge or by means of gavage and nebulization. Treatments with both ciglitazone and GW9662, a specific antagonist, were also performed to verify that ciglitazone's effects were mediated through PPAR-gamma activation. RESULTS: Our results show that PPAR-gamma is mainly expressed in airway epithelium on antigen sensitization. Treatment with ciglitazone reduced PPAR-gamma levels in the lung, whereas combined treatment with GW9662 abrogated this inhibition. Importantly, nebulization with ciglitazone decreased airway hyperresponsiveness, basement membrane thickness, mucus production, collagen deposition, and TGF-beta synthesis. A significant correlation was also found between airway hyperresponsiveness, basement membrane thickness, and TGF-beta levels. CONCLUSION: These results demonstrate that inhaled agonistic ligands of PPAR-gamma might have new therapeutic potential for airway asthmatic inflammation. 相似文献
92.
Azelastine, a newly synthesized anti-allergic agent, was tested for its effects on guinea pig macrophage chemotaxis and phagocytosis. As specific macrophage chemo-attractants, we used macrophage chemotactic factors a and c; separated and highly purified from inflamed skin sites. Macrophage chemotaxis induced by skin extract or chemotactic factors was significantly suppressed by a low concentration of the agent (1 microgram/ml); the effect was dose-dependent. The inhibition of chemotaxis was reversible, because chemotactic activity was restored when the agents was removed by washing cells before chemotactic assay. Inactivation of chemotactic factors was not detected by mixing azelastine and factors a and c. Azelastine may directly interact with macrophages to decrease their chemotactic responsiveness. beta-Glucuronidase activity in the medium and macrophages after phagocytosis of polystyrene latex particles was not affected by this agent at concentrations ranging from 1 to 10 micrograms/ml. The phagocytosis of latex particles or sheep red blood cells opsonized with IgG antibodies (EA) and anchoring of macrophages to substrate were not inhibited and azelastine did not damage the macrophages as determined by lactate dehydrogenase (LDH) release assay. 相似文献
93.
Tissue regeneration using macrophage migration inhibitory factor-impregnated gelatin microbeads in cutaneous wounds
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Zhao Y Shimizu T Nishihira J Koyama Y Kushibiki T Honda A Watanabe H Abe R Tabata Y Shimizu H 《The American journal of pathology》2005,167(6):1519-1529
Migration inhibitory factor (MIF) responds to tissue damage and regulates inflammatory and immunological processes. To elucidate the function of MIF in cutaneous wound healing, we analyzed MIF knockout (KO) mice. After the excision of wounds from the dorsal skin of MIF KO and wild-type (WT) mice, healing was significantly delayed in MIF KO mice compared to WT mice. Lipopolysaccharide treatment significantly increased [(3)H]thymidine uptake in WT mouse fibroblasts compared to MIF KO mouse fibroblasts. Furthermore, there was a significant reduction in fibroblast and keratinocyte migration observed in MIF KO mice after 1-oleoyl-2-lysophosphatidic acid treatment. We subsequently examined whether MIF-impregnated gelatin slow-release microbeads could accelerate skin wound healing. Injection of more than 1.5 microg/500 microl of MIF-impregnated gelatin microbeads around a wound edge accelerated wound healing compared to a single MIF injection without the use of microbeads. MIF-impregnated gelatin microbeads also accelerated skin wound healing in C57BL/6 mice and diabetic db/db mice. Furthermore, incorporating MIF-impregnated gelatin microbeads into an artificial dermis implanted into MIF KO mice accelerated procollagen production and capillary formation. These findings suggest that MIF is crucial in accelerating cutaneous wound healing and that MIF-impregnated gelatin microbeads represent a promising treatment to facilitate skin wound healing. 相似文献
94.
H Yoshimura H Uchida H Ohishi N Honda S Ohue Y Kinoshita M Katsuragi N Matuso Y Hosogi M Hatakeyama 《European journal of radiology》1986,6(3):195-198
The hepatic arteries of 122 patients were analysed on angiography to identify the left medial segment of the liver. Left medial arterial branches were classified into three types: type I arising from the left hepatic artery on the umbilical portion of the portal vein; type II arising from proximal portion of left hepatic artery before reaching the umbilical portion of the portal vein; type III arising from right hepatic artery. Incidence of each type is 37.2%, 35.8% and 27.0%, respectively. The artery frequently kinks at the right side of the umbilical portion of the portal vein and a total of incidence is 68% and that of each type is 23.5%, 89.8% and 100%, respectively. We call this characteristic kinking point of the left medial arterial branches, the "M-point". 相似文献
95.
Malnutrition is a core symptom of the frailty cycle in older adults. The purpose of this study was to investigate whether dysphagia influences nutrition or frailty status in community-dwelling older adults. The study participants were 320 Japanese community-dwelling older adults aged ≥65 years. All participants completed a questionnaire survey that included items on age, sex, family structure, self-rated health, nutritional and frailty status, and swallowing function. Nutritional status was categorized as malnourished, at risk of malnutrition, and well-nourished based on the Mini Nutrition Assessment-Short Form. The participants were then classified into a malnutrition (malnourished/at risk) or a well-nourished group (well-nourished). Frailty was assessed using the Cardiovascular Health Study criteria. The participants were then divided into a frailty (frail/pre-frail) or a non-frailty group (robust). Dysphagia was screened using the 10-item Eating Assessment Tool. Multiple logistic regression analysis was conducted to determine whether dysphagia was associated with nutritional or frailty status. The results revealed that dysphagia influenced both nutrition (odds ratio [OR]: 4.0; 95% confidence interval [CI]: 1.9–8.2) and frailty status (OR: 2.3; 95% CI: 1.0–5.2); therefore, the swallowing function would be an important factor for community-dwelling older adults on frailty prevention programs. 相似文献
96.
97.
The relationships between increases in body mass index (BMI) and increases in hypertension were compared between non-drinkers with elevated serum gamma-glutamyl transpeptidase (gamma-GTP) levels (> or = 50 U/l) and those with normal levels, who comprised 10,952 men and 22,107 women aged 40-59 years recruited from an occupational health clinic. Hypertension was found in 16.1% and 13.5% of the men and women, and elevated serum g-GTP was found in 10.8% and 2.8% of the men and women, respectively. The prevalences of hypertension and elevated serum gamma-GTP levels were both increased with increased BMI. Hypertension was, however, shown to be 1.5 times more prevalent in the persons with elevated serum gamma-GTP levels than in those with normal levels in both sexes, even after adjusting for BMI by a multiple logistic analysis. It can be concluded that elevations of serum gamma-GTP, which are probably a reflection of fatty liver in the non-drinkers, are closely related to the development of hypertension associated with increased obesity. 相似文献
98.
Takafumi Ichida Masashi Kato Akihito Hayakawa Shinichi Ito Shigeki Mori Tomomi Sato Souichi Sugitani Hiroshi Sato Masashi Watanabe Hitoshi Asakura 《Cancer chemotherapy and pharmacology》1994,33(Z1):S74-S78
Prior injection of an anticancer agent and Lipiodol mixture is a key point for the treatment of hepatocellular carcinoma (HCC). We therefore prepared a new, improved emulsion of Lipiodol containing a high dose ofcis-diamminedichloroplatinum (CDDP) and epirubicin by replacing the ionic contrast medium (Urografin 67) with a nonionic contrast medium (Iopamidol; Iopamiron 300) and adding phosphatidyl choline. This CDDP-epirubicin-Lipiodol emulsion (CELE) was examined pharmacologically and chemically with the following results. The size of these particles is less than 10 m (diameter) for up to 24 h; the release of 28%–34% of the CDDP and 80%–90% of the epirubicin was estimated in the dissolution test, and 85% of the CDDP and 35% of the epirubicin was retained in the organs in the moment calculation. CELE was injected into 58 HCC patients via a celiac angiographic catheter. In 36 of these patients, the CELE injection was followed by transcatheter arterial embolization (TAE) therapy. Following the administration of CELE as one-shot injection therapy for stage IV HCC, the 1-year survival rate was 59% and the 2-year survival rate was 27%. Moreover, in patients (stage II, 12; stage III, 8; stage IV, 16) who received CELE and subsequently underwent TAE therapy, the 1-year survival rate was 90% and the 2-year survival rate was 67%. The nonionic contrast medium with Lipiodol forms finer emulsified particles, and these particles are more capable of penetrating into the tumor. In addition, the greater pharmacological stability of these particles provides a slow-release effect and prolonged stability of their shape. Finally, theoretically, the use of two major anticancer agents such as CDDP and epirubicin showed a greater clinical effect in the treatment of HCC than either our earlier suspension or a single anticancer agent.Work presented at the Third International Symposium on Treatment of Liver Cancer, Seoul, Korea, 12–13 February 1993 相似文献
99.
Jun Nawata Yasunori Toyoda Hirokazu Nisihira Kohjiro Honda Hisato Kigasawa Takeshi Nagao 《European journal of pediatrics》1994,153(5):325-327
A 6-year-old girl with post-hepatitic severe aplastic anaemia was referred to our hospital. Haematological examination showed a haemoglobin level of 5.2 g/dl, platelet count of 8,000/l, and white blood cell count of 130/l with 17% neutrophils. She was treated with recombinant human granulocytecolony stimulating factor (15 g/kg/day i.v.) and cyclosporin A (6 mg/kg/day p.o.). The absolute neutrophil count gradually increased, but Hb and platelets were not improved. The intravenous administration of recombinant human erythropoietin (100 U/kg three times a week) was started, and the reticulocyte count reached 20000/l on day 12. The platelets increased to 81000/l after 16 months of combined administration of recombinant human granulocyte-colony stimulating factor, recombinant human erythropoietin and cyclosporin A. After 20 months of combined administration, the haematological results were: Hb, 13.1 g/dl; platelets 80000/l: WBC, 9500/l with 40% neutrophils. After recombinant human granulocyte-colony stimulating factor treatment, the myeloid elements of the bone marrow and the number of granulocyte-macrophage colony forming units increased. Bone marrow erythropoiesis and erythroid colonies also increased after recombinant human erythropoietin administration. The clinical course suggested a beneficial effect of haemopoietic growth factors and cyclosporin A in post-hepatitic aplastic anaemia. 相似文献
100.
In order to elucidate the cause of body weight loss in the early stage of tumor progression, morphological changes of striated muscle were investigated in rabbits every 10 days after VX2 carcinoma implantation. The lean body mass started to decrease in the tumor-bearing rabbits 10 days after implantation, and body fat ratio showed a significant decrease from 30 days, different from the starved rabbits, whose lean body mass and body fat ratio started to decrease from 10 days. Morphological hallmarks of apoptosis in muscle cells were detected in tumor-bearing animals prior to the tumor growth but not in starved animals. These findings suggest that muscle cell apoptosis may be responsible for the body weight loss in the early tumor-bearing. 相似文献