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61.
Koji Fukushima Yoshiyuki Ueno Hirokazu Kanegane Yoko Yamagiwa Jun Inoue Osamu Kido Futoshi Nagasaki Takayuki Kogure Eiji Kakazu Yu Nakagome Yasunori Matsuda Noriyuki Obara Osamu Kimura Tooru Shimosegawa 《Hepatology research》2008,38(4):415-420
Severe hepatitis with an indistinct etiology manifested in a 16-year-old boy who had no particular history. The histological features of the liver and clinical course of the patient were similar to those of patients with autoimmune hepatitis characterized by interface hepatitis and severe lobular inflammation of the liver and recurrent exacerbations of hepatitis. We administered intravenous glycyrrhizin preparation daily or three times a week combined with the oral administration of ursodeoxycholic acid daily throughout the term after the initial onset of disease for the control of disease activity. The normalization of the concentration of alanine aminotransferase in serum was achieved in response to the therapy during the course. The serum concentration of immunoglobulins of the patient gradually decreased from the onset of the disease to an unacceptable level without globulin preparation during the following period of 17 months. Immunological tests revealed impairment of immunoglobulin production bythe B cell population of the patient, which led to the diagnosis of the patient as common variable immunodeficiency (CVID). The patient, with improved liver histology after 27 months from the onset of disease, benefited from the current combination therapy without severe infection through the avoidance of overimmunosuppression. CVID is defined as a heterogeneous syndrome characterized by various degrees of hypogammaglobulinemia without any specific predisposing causes, frequently associated with autoimmunity. Diagnostic criteria and therapeutic options of persistent hepatitis with CVID are to be established, as discussed in the current report. 相似文献
62.
Yuya Yoshimoto Takahiro Oike Noriyuki Okonogi Yoshiyuki Suzuki Ken Ando Hiro Sato Shin-ei Noda Mayu Isono Kousaku Mimura Koji Kono Takashi Nakano 《Journal of radiation research》2015,56(3):509-514
X-ray radiotherapy activates tumor antigen-specific T-cell responses, and increases in the serum levels of high mobility group box 1 (HMGB1) induced by X-ray irradiation play a pivotal role in activating anti-tumor immunity. Here, we examined whether carbon-ion beams, as well as X-rays, can induce HMGB1 release from human cancer cell lines. The study examined five human cancer cell lines: TE2, KYSE70, A549, NCI-H460 and WiDr. The proportion of cells surviving X- or carbon-ion beam irradiation was assessed in a clonogenic assay. The D10, the dose at which 10% of cells survive, was calculated using a linear–quadratic model. HMGB1 levels in the culture supernatants were assessed by an ELISA. The D10 dose for X-rays in TE2, KYSE70, A549, NCI-H460 and WiDr cells was 2.1, 6.7, 8.0, 4.8 and 7.1 Gy, respectively, whereas that for carbon-ion beams was 0.9, 2.5, 2.7, 1.8 and 3.5 Gy, respectively. X-rays and carbon-ion beams significantly increased HMGB1 levels in the culture supernatants of A549, NCI-H460 and WiDr cells at 72 h post-irradiation with a D10 dose. Furthermore, irradiation with X-rays or carbon-ion beams significantly increased HMGB1 levels in the culture supernatants of all five cell lines at 96 h post-irradiation. There was no significant difference in the amount of HMGB1 induced by X-rays and carbon-ion beams at any time-point (except at 96 h for NCI-H460 cells); thus we conclude that comparable levels of HMGB1 were detected after irradiation with iso-survival doses of X-rays and carbon-ion beams. 相似文献
63.
Matsumoto M Zhou Y Matsuo S Nakanishi H Hirose K Oura H Arase S Ishida-Yamamoto A Bando Y Izumi K Kiyonari H Oshima N Nakayama R Matsushima A Hirota F Mouri Y Kuroda N Sano S Chaplin DD 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(18):6720-6724
Controlled proteolytic degradation of specialized junctional structures, corneodesmosomes, by epidermal proteases is an essential process for physiological desquamation of the skin. Corneodesmosin (CDSN) is an extracellular component of corneodesmosomes and, although considerable debate still exists, genetic studies have suggested that the CDSN gene in the major psoriasis-susceptibility locus (PSORS1) may be responsible for susceptibility to psoriasis, a human skin disorder characterized by excessive growth and aberrant differentiation of keratinocytes. CDSN is also expressed in the inner root sheath of hair follicles, and a heterozygous nonsense mutation of the CDSN gene in humans is associated with scalp-specific hair loss of poorly defined etiology. Here, we have investigated the pathogenetic roles of CDSN loss of function in the development of skin diseases by generating a mouse strain with targeted deletion of the Cdsn gene. Cdsn-deficient mouse skin showed detachment of the stratum corneum from the underlying granular layer and/or detachment within the upper granular layers due to the disrupted integrity of the corneodesmosomes. When grafted onto immunodeficient mice, Cdsn-deficient skin showed rapid hair loss together with epidermal abnormalities resembling psoriasis. These results underscore the essential roles of CDSN in hair physiology and suggest functional relevance of CDSN gene polymorphisms to psoriasis susceptibility. 相似文献
64.
Hyperglycemia increases oxidative stress in various tissues and leads to diabetic cardiovascular complication. Dyslipidemia,
such as an increase in oxidized low-density lipoprotein (LDL), is well recognized in diabetic patients with hyperglycemia.
However, the mechanism by which hyperglycemia causes the increased LDL oxidation remains unclear. Albumin is the most abundant
protein in the circulation, and can function as an antioxidant. Therefore, we examined whether glycoxidative modification
inhibits the antioxidant activity of albumin to LDL oxidation and clarified the mechanism by which this modification may suppress
its antioxidant activity. Human serum albumin (HSA) was incubated in phosphate-buffered saline with and without glucose at
37°C for up to 8 weeks under aerobic conditions (referred to as glycoxidation (goHSA) and oxidation (oHSA), respectively).
Metal chelator-treated, nonoxidative HSA (chHSA) and freshly prepared HSA (fHSA) were used as controls. N
ε-(carboxymethyl)lysine (CML), a glycoxidative product, was determined by enzyme-linked immunosorbent assay. Oxidation was
estimated by measuring the thiols of the HSA molecule. Copper-mediated oxidation of LDL was conducted in the presence or absence
of modified HSAs at 37°C for 6 days. Malondialdehyde and negative charge of LDL were measured. To clarify the mechanism of
reduced antioxidant activity of HSA, we examined firstly the binding activity of modified HSAs to copper, and secondly the
effects of free radical scavengers on the formation of malondialdehyde. CML was formed in goHSA in a time- and concentration-dependent
manner. Both goHSA and oHSA significantly decreased the contents of free thiol groups compared to ch- and fHSAs. The antioxidant
activity of goHSA to LDL oxidation was the lowest among various modified HSAs. The oHSA showed a moderate decrease in antioxidant
activity. The binding activity of go- and oHSAs to copper was lower than that of ch- and fHSAs. The formation of MDA from
LDL oxidation in the presence of goHSA was completely inhibited by Tiron (1,2-dihydroxy-3,5-benzenedisulfonic acid) and superoxide
dismutase. In contrast, catalase and mannitol had no effect. Our results indicate that in vitro glycoxidation of HSA induced
a marked loss of antioxidant activity of this molecule to copper-mediated oxidation of LDL, which may be caused by the generation
of superoxide.
Received: December 17, 2001 / Accepted: June 28, 2002
Acknowledgments The authors thank Drs. Ryoji Nagai and Seikoh Horiuchi (Department of Biochemistry, Kumamoto University School of Medicine,
Kumamoto, Japan) and Drs. Hiroyuki Itabe and Tatsuya Takano (Department of Microbiology and Molecular Pathology, Faculty of
Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, Japan) for kindly supplying antibodies. We also thank Associate
Professor Takeo Yamaguchi (Department of Chemistry, Faculty of Science, Fukuoka University) for the ESR experiment and Miss
Satoko Nagano for her excellent technical assistance. This work was supported by a Grant-in-Aid from the Ministry of Education,
Science, Sports and Culture of Japan (No. 14570171) and in part by funds from the Central Research Institute of Fukuoka University
(No. 016004).
Correspondence to N. Sakata 相似文献
65.
Tetsutaro Nagaoka Yasuhiro Setoguchi Masashi Muramatsu Noriyuki Honma Takashi Danbara Hideaki Miyamoto Hiroshi Izumi Toshimasa Uekusa Yoshinosuke Fukuchi 《Nihon Kokyūki Gakkai zasshi》2002,40(6):525-529
A 71-year-old man was referred to our hospital complaining of cough. Chest radiography revealed a mass opacity in the right upper lung field. A transbronchial biopsy specimen revealed non-specific inflammatory changes. Percutaneous lung aspiration biopsy under ultrasound guidance demonstrated gram-positive rods, suggesting actinomyces. On the diagnosis of pulmonary actinomycosis, the patient was treated with penicillin-G and his symptoms were relieved. In a three-month follow-up, the mass shadow in the right upper lung field was found to have increased in size. Squamous cell lung cancer was diagnosed on the basis of repeated transbronchial tumor biopsies, and right upper lobectomy was performed. Most cases of pulmonary actinomycosis have been diagnosed from post-surgical tumor specimens taken on suspicion of the presence of lung cancer. However, the lung cancer in this case was difficult to diagnose because the lung cancer was co-existent with pulmonary actinomycosis. 相似文献
66.
Takaomi Adachi Noriyuki Sugiyama Tatsuro Gondai Hideo Yagita Takahiko Yokoyama 《ACTA HISTOCHEMICA ET CYTOCHEMICA》2013,46(6):161-170
Renal ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI). Many investigators have reported that cell death via apoptosis significantly contributed to the pathophysiology of renal IRI. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily, and induces apoptosis and inflammation. However, the role of TRAIL in renal IRI is unclear. Here, we investigated whether TRAIL contributes to renal IRI and whether TRAIL blockade could attenuate renal IRI. AKI was induced by unilateral clamping of the renal pedicle for 60 min in male FVB/N mice. We found that the expression of TRAIL and its receptors were highly upregulated in renal tubular cells in renal IRI. Neutralizing anti-TRAIL antibody or its control IgG was given 24 hr before ischemia and a half-dose booster injection was administered into the peritoneal cavity immediately after reperfusion. We found that TRAIL blockade inhibited tubular apoptosis and reduced the accumulation of neutrophils and macrophages. Furthermore, TRAIL blockade attenuated renal fibrosis and atrophy after IRI. In conclusion, our study suggests that TRAIL is a critical pathogenic factor in renal IRI, and that TRAIL could be a new therapeutic target for the prevention of renal IRI. 相似文献
67.
Ikuko Haruta Etsuko Hashimoto Ikuko Haruta Etsuko Hashimoto Noriyuki Shibata Ikuko Haruta 《Autoimmunity》2013,46(5):372-379
Background: Chronic colitis-harboring TCRα? / ? × AIM? / ? mice showed PBC-like bile duct damage in the liver. Bacterial infection is one of the candidates for the pathogenesis of PBC. We demonstrated that the bacterial cell wall component lipotheicoic acid (LTA) was detected at sites of inflammation around damaged bile ducts in PBC patients. The aim of this study was to investigate the pathophysiology of the liver and other organs in TCRα? / ? × AIM? / ? mice.Methods: Thirteen female TCRα? / ? × AIM? / ? mice were sacrificed at 24 weeks of age. The liver, stomach, small intestine, colon, pancreas, kidney and spleen were studied for pathological examination. Using anti-LTA antibody as the primary antibody, an immunohistochemical study was carried out.Results: In the liver, LTA was mainly detected in the portal area with inflammation, and some of the cytoplasm of hepatocytes. Inflammations were also observed in the stomach, intestine, pancreas and kidney. Throughout the gastrointestinal tract, from the stomach to the colon, LTA was detected in the epithelium at sites of inflammation. Furthermore, LTA was detected around both pancreatic ducts with inflammation and distal renal tubules with inflammation.Conclusions: The development of inflammations in the liver as well as extensive organs, strongly suggests a close relationship between bile duct damage and systemic multifocal epithelial inflammations, perhaps involving bacterial LTA, in TCRα? / ? × AIM? / ? mice. 相似文献
68.
Hiroo Takahashi Kaichiro Sawada Takatoshi Kakuta Takao Suga Kazuya Hanai Genta Kanai Satoshi Fujimura Noriyuki Sanechika Toshiro Terachi Masafumi Fukagawa Akira Saito 《Journal of artificial organs》2013,16(3):368-375
Bioartificial renal tubule devices (BTD) use cell therapy to improve conditions commonly observed in recipients of artificial kidneys for treatment of kidney diseases. We previously reported significant improvement of the condition of acute kidney injury (AKI) animals after treatment with BTD prepared with lifespan-extended human renal proximal tubular cells (hRPTEC). However, a major obstacle to use of BTD for patients is their biological safety, because hRPTEC are cultured in medium containing fetal calf serum. To establish the biological safety of BTD, we prepared BTD with lifespan-extended hRPTEC cultured in a newly developed serum-free medium and compared these with BTD prepared with hRPTEC cultured in serum-containing conventional medium. Lifespan-extended hRPTEC cultured in serum-free medium (hRPTEC-SFM) can proliferate similar to hRPTEC cultured in serum-containing conventional medium (hRPTEC-CM). Comparison of leakage and of reabsorption of small molecules for BTD prepared with hRPTEC-SFM (BTD-SFM) with those for our previous BTD prepared with hRPTEC-CM (BTD-CM) showed transportation in these two types of BTD was almost identical. When AKI goats were treated with BTD-SFM for 26 h, increase of survival time and reduction of cytokine expression in blood cells were almost same as for AKI goats treated with BTD-CM. Quantification of the expression of some genes of hRPTEC in BTD revealed significant changes during BTD treatment for AKI goats. In conclusion, lifespan-extended hRPTEC-SFM work as well as hRPTEC-CM, and the biological safety of BTD for patients could be elevated without loss of function by preparation from hRPTEC-SFM. 相似文献
69.
70.
Inamochi Yuka Fueki Kenji Matsuyama Yusuke Yoshida-Kohno Eiko Fujiwara Takeo Wakabayashi Noriyuki 《Clinical oral investigations》2020,24(8):2603-2609
Clinical Oral Investigations - This study aimed to determine if oral dryness is associated with oral pain sensitivity in removable denture wearers. The pressure pain threshold (PPT) in the mucosa... 相似文献