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101.
102.
Sugimoto T Ito J Takeda N Gasyu I Okazaki T Sakaguchi M Osawa N Tanaka Y Oka K Uzu T Kashiwagi A 《The American journal of the medical sciences》2008,335(6):495-498
Castleman's disease is a rare atypical lymphoproliferative disorder. Renal manifestations, such as proteinuria, hematuria, and renal dysfunction, are common in Castleman's disease; however, a nephrotic syndrome rarely occurs. We have encountered an unusual case of Castleman's disease of the plasma cell type characterized by nephrotic syndrome because of glomerulopathy mimicking membranoproliferative glomerulonephritis. Our patient showed higher levels of circulating cytokines (interleukin-6/vascular endothelial cell-derived growth factor), the glomerular lesions not associated with immunocomplex deposition, and the resolution of nephrotic syndrome after successful corticosteroids therapy resulting in a decline in cytokines levels, thereby implicating a cytokine-induced glomerular cell injury/activation as a possible cause of the glomerular pathological changes in this case. 相似文献
103.
Kuriyama M Kato J Kuwaki K Morimoto N Nawa T Fujimoto T Kono H Okano N Miyaike J Morita T Okada H Suzuki S Yoshioka T Shiode J Suwaki K Sakaguchi K Shiratori Y;Japan West Ulcerative Colitis Study Group 《European journal of gastroenterology & hepatology》2008,20(7):634-641
BACKGROUND AND AIM: The health-related quality of life (HRQOL) of patients with ulcerative colitis (UC) can be impaired because of the chronic symptoms. Although UC patients suffer from such symptoms over the long term, there have been few reports on the changes of HRQOL with disease duration. The aim of this study was to clarify these changes. METHODS: The HRQOL of 331 Japanese UC patients was examined using the validated Japanese version of the Inflammatory Bowel Disease Questionnaire (J-IBDQ). HRQOL and factors affecting HRQOL identified using multiple linear regression analysis were stratified by disease duration. RESULTS: Of the 15 clinical factors examined, the clinical activity index score was the strongest determinant (P<0.0001) of all the scores of IBDQ regardless of disease duration. HRQOL did not differ significantly among patients with different disease durations. The factors, however, that affected HRQOL varied according to disease duration. In patients with disease duration of less than 5 years, the clinical activity index score was the predominant factor affecting HRQOL. Being 'on sick leave or hospitalized' was a significant factor impairing HRQOL in patients with disease duration of 5-9 years. Moreover, complications due to corticosteroids significantly impaired all of the IBDQ scores in patients with disease duration of 10 years or more. CONCLUSION: Factors that affected the HRQOL of UC patients varied according to the patients' disease duration. Our findings should assist in the development of a long-term strategy for the treatment of UC patients. 相似文献
104.
Shiratori Y Kato N Yoshida H Nakata R Ihori M Imazeki F Yokosuka O Kawase T Katamoto T Unuma T Nakamura A Ikegami F Hirota K Omata M 《Digestive diseases and sciences》2000,45(3):565-574
Adequate dosing of interferon (IFN) and its cost-effectiveness for sustained virological response were evaluated in relation to viral load and subtype. Prospective analysis of IFN therapy on 326 patients with chronic hepatitis C free from cirrhosis was performed using 9 or 6 million unit (MU) of IFN for six months daily and/or three times a week. Sustained virological response was achieved in 50–94% of patients with 2 × 104 copies/ml (competitive RT-PCR) or <100 × 103 copies/ml (Amplicor monitor) of HCV RNA by 468–1206 MU of IFN, but response was only 0–25% of the patients with 2 × 105.5 copies/ml (competitive RT-PCR) or >200 × 103 copies/ml (Amplicor monitor), even with 468–1206 MU of IFN. A high sustained rate was demonstrated in patients with 100–200 × 103 copies/ml of HCV RNA by 901–1206 MU of IFN, in comparison to that with 900 MU of IFN. Multivariate analysis showed that IFN dose had a significant value for the efficacy of IFN therapy in patients presenting 100–200 × 103 copies/ml of HCV RNA. Cost efficacy analysis indicated that it cost approximately $10,000, $26,000, and $50,000–227,000 for one person-viral eradication in the patients with <100, 100–200, and >200 × 103 copies/ml, respectively. High-dose IFN is only cost effective in patients with intermediate viral loads, and IFN therapy could be recommended in patients with <200 × 103 copies/ml of HCV RNA. 相似文献
105.
Accumulation of cholera toxin and GM1 ganglioside in the early endosome of Niemann–Pick C1-deficient cells 下载免费PDF全文
Yuko Sugimoto Haruaki Ninomiya Yuki Ohsaki Katsumi Higaki Joanna P. Davies Yiannis A. Ioannou Kousaku Ohno 《Proceedings of the National Academy of Sciences of the United States of America》2001,98(22):12391-12396
We investigated intracellular trafficking of GM1 ganglioside in Niemann-Pick C1 (NPC1)-deficient Chinese hamster ovary cells [NPC1(-) cells] by using cholera toxin (CT) as a probe. Both the holotoxin and the B subunit (CTB) accumulated in GM1-enriched intracellular vesicles of NPC1(-) cells. CTB-labeled vesicles contained the early endosome marker Rab5 but not lysosome-associated membrane protein 2 and were not labeled with either Texas red-transferrin or Lysotracker, indicating that they represent early endosomes. Similarly, CT accumulated in intracellular vesicles of human NPC fibroblasts that contained both Rab5 and early endosomal antigen 1. CTB accumulation in NPC1(-) cells was abolished by expression of wild-type NPC1 but not by mutant proteins with a mutation either in the NPC domain or the sterol-sensing domain. A part of these mutant NPC1 proteins expressed in NPC1(-) cells was localized on CTB-labeled vesicles. U18666A treatment of "knock in" cells [NPC1(-) cells that stably expressed wild-type NPC1] caused CTB accumulation similar to that in NPC1(-) cells, and a part of wild-type NPC1was localized on CTB-labeled vesicles in drug-treated cells. Finally, CT tracer experiments in NPC1(-) cells revealed retarded excretion of internalized toxin into the culture medium and an increase in the intracellular release of A subunits. In accordance with the latter result, CT was more effective in stimulating cAMP formation in NPC1(-) than in wild-type cells. These results suggest that transport of CT/GM1 complexes from the early endosome to the plasma membrane depends on the function of NPC1, whereas transport to the Golgi apparatus/endoplasmic reticulum does not. 相似文献
106.
Targeted mutations of the juxtamembrane tyrosines in the Kit receptor tyrosine kinase selectively affect multiple cell lineages 总被引:3,自引:0,他引:3 下载免费PDF全文
Kimura Y Jones N Klüppel M Hirashima M Tachibana K Cohn JB Wrana JL Pawson T Bernstein A 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(16):6015-6020
Loss-of-function mutations in the murine dominant white spotting/c-kit locus affect a diverse array of biological processes and cell lineages and cause a range of phenotypes, including severe anemia, defective pigmentation, sterility, mast cell deficits, a lack of interstitial cells of Cajal, spatial learning memory deficits, and defects in peripheral nerve regeneration. Here we show that tyrosine residues 567 and 569 in the juxtamembrane (Jx) domain of the murine Kit receptor tyrosine kinase are crucial for the function of Kit in melanogenesis and mast cell development, but are dispensable for the normal development of erythroid, interstitial cells of Cajal and germ cells. Furthermore, adult mice lacking both tyrosines exhibit splenomegaly, dysregulation of B-cell and megakaryocyte development, and enlarged stomachs. Analysis of signal transduction events induced by the mutant receptors after ligand stimulation indicates that Jx tyrosine mutations diminish receptor autophosphorylation and selectively attenuate activation of extracellular signal-regulated kinase/mitogen-activated protein kinases. Together, these observations demonstrate that the Jx domain of Kit plays a cell-type specific regulatory role in vivo and illustrate how engineered mutations in Kit can be used to understand the complex biological and molecular events that result from activating a receptor tyrosine kinase. 相似文献
107.
Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis 总被引:5,自引:0,他引:5
Nakamura M Shimizu-Yoshida Y Takii Y Komori A Yokoyama T Ueki T Daikoku M Yano K Matsumoto T Migita K Yatsuhashi H Ito M Masaki N Adachi H Watanabe Y Nakamura Y Saoshiro T Sodeyama T Koga M Shimoda S Ishibashi H 《Journal of hepatology》2005,42(3):386-392
BACKGROUND/AIMS: The presence of antibodies to the 210-kDa glycoprotein of the nuclear pore complex (gp210) is highly indicative of primary biliary cirrhosis (PBC). However, the significance of anti-gp210 antibody titers for monitoring PBC remains unresolved. METHODS: We used an ELISA with a gp210 C-terminal peptide as an antigen to assess serum antibody titers in 71 patients with PBC. RESULTS: Patients were classified into three groups: Group A in whom anti-gp210 titers were sustained at a high level, Group B in whom anti-gp210 status changed from positive to negative under ursodeoxycholic acid (UDCA) therapy, Group C in whom anti-gp210 antibodies were negative at the time of diagnosis. The rate of progression to end-stage hepatic failure was significantly higher in group A (60%) as compared to groups B (0%) and C (4.2%). The sustained antibody response to gp210 was closely associated with the severity of interface hepatitis. The significance of anti-gp210 antibody was confirmed by National Hospital Organization Study Group for Liver Disease in Japan. CONCLUSIONS: The serial quantitation of serum anti-gp210-C-terminal peptide antibodies is useful for monitoring the effect of UDCA and for the early identification of patients at high risk for end-stage hepatic failure. 相似文献
108.
Yuki Kato Masayuki Ninomiya Yuji Yamaguchi Mamoru Koketsu 《Medicinal chemistry research》2015,24(3):1180-1188
Hyaluronidase is one of the most important enzymes in the development of many diseases. In this study, a series of xyloside analogues bearing a triazole and tetrazole at the anomeric position were prepared from xylosylthioureas and evaluated their inhibitory effects on the hyaluronidase. Triazole and tetrazole skeletons were formed via the Hg(OAc)2-mediated desulfurizative cyclization through carbodiimide intermediates. According to in vitro anti-hyaluronidase assay, tetrazole-xylosides having p-chloro- or p-nitro-substitution exhibited the high inhibition rates, whereas the compound having p-trifluoromethyl group on the structure did not show the potency. Our results demonstrated the importance of tetrazole-xylosides as hyaluronidase inhibitors. 相似文献
109.
Yuki Otani Hidefumi Mukai Yuki Fuchigami Fumiyoshi Yamashita Mitsuru Hashida 《Journal of drug targeting》2015,23(5):427-435
Background: Achieving long-term gene expression in kidney will be beneficial for gene therapy of renal and congenital diseases, genetic studies constructing animal disease models, and the functional analysis of disease-related genes.Purpose: The purpose of this study was to develop an in vivo long-term gene expression system in murine kidney using ?C31 integrase.Methods: Gene expression in cultured RENCA, TCMK-1, and HEK293 cells was assessed. The long-term in vivo gene expression system in the kidney was achieved by co-transfecting 5?µg of pORF-luc/attB as a donor plasmid and 20?µg of pCMV-luc as a helper plasmid into the right kidney of mice by electroporation. Luciferase expression levels were measured to determine longevity of the expression.Results: Significantly high luciferase expression levels were observed in cultured RENCA, TCMK-1, and HEK293 cells over 1 month compared with controls (non-integrase system). The luciferase cDNA sequence was integrated at a pseudo attP site termed mpsL1. In vivo luciferase expression levels in the integrase group were sustained and significantly higher than those in the control group over 2 months. Furthermore, ?C31 integrase-transfected cells had less genomic DNA damage caused by integrase expression.Discussion and conclusion: These results demonstrated that the ?C31 integrase system could produce long-term (2 months) in vivo gene expression in mouse kidney. 相似文献
110.
Mayu Yazaki Takeru Nabeta Takayuki Inomata Kenji Maemura Takumi Oki Teppei Fujita Yuki Ikeda Shunsuke Ishii Takashi Naruke Yusuke Inoue Junya Ako 《Clinical cardiology》2021,44(2):222
BackgroundClinical significance of left atrial (LA) function and geometry in patients with dilated cardiomyopathy (DCM) remains uncertain.HypothesisLA geometric parameters assessed by cardiac magnetic resonance (CMR) predict the prognosis in patients with DCM.MethodsThe present study included patients with DCM and sinus rhythm who underwent CMR between December 2007 and April 2018. LA volume was measured using CMR. LA sphericity index was computed as the ratio of the measured maximum LA volume by the volume of a sphere with maximum LA length diameter.ResultsWe included 255 patients in this study. During the mean follow‐up of 3.92 years, hospitalization for HF occurred in 37 patients. The LA sphericity index was significantly higher in patients with hospitalization for HF than in those without (0.78 ± 0.35 vs. 0.58 ± 0.18, p < .001). Multivariable Cox regression analysis identified a higher LA sphericity index as an independent predictor of hospitalization for HF. Patients were categorized based on the median of LA sphericity index. The Kaplan–Meier curve showed that patients with a high LA sphericity index (≥0.57) had a significantly higher risk of hospitalization for HF than those with a low LA sphericity index (<0.57).ConclusionLA sphericity index was an independent predictor of hospitalization for HF. Assessment of LA geometric parameters might be useful for risk stratification in patients with DCM. 相似文献