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51.
Frequencies of inherited organic acidurias and disorders of mitochondrial fatty acid transport and oxidation in Germany 总被引:6,自引:0,他引:6
Hoffmann GF von Kries R Klose D Lindner M Schulze A Muntau AC Röschinger W Liebl B Mayatepek E Roscher AA 《European journal of pediatrics》2004,163(2):76-80
The lack of epidemiological data on the frequency and/or burden of organic acidurias (OA) and mitochondrial fatty acid transport and oxidation disorders (mtFATOD) is one reason for hesitation to expand newborn screening (NBS) by tandem mass spectrometry (MS-MS). From 1999 to 2000, the frequency of ten potentially treatable OA and mtFATOD was assessed by active nation-wide surveillance on cases presenting with clinical symptoms using the German Paediatric Surveillance Unit (ESPED) system. Case ascertainment was complemented by a second independent source: 3-monthly inquiries in the metabolic laboratories performing secondary selected screening for OA and mtFATOD. Frequency estimates for clinically symptomatic cases older than 7 days in a birth cohort of 844,575 conventionally screened children was compared to the frequency found in a cohort of 382,247 screened by MS-MS in Bavaria and Baden-Württemberg. The overall frequency of the ten conditions considered was 1:8,000 (95% CI 1:11,000–1:6,000) by MS-MS as compared to 1:23,000 (95% CI 1:36,000–1:17,000) in symptomatic cases presenting mainly with metabolic crisis. The contributions of medium-chain acyl-CoA dehydrogenase deficiency (MCADD), other mtFATOD and OA were 29, 4 and 13 among the 46 cases identified by MS-MS, and 19, 1 and 13 among the 33 clinically symptomatic cases, respectively. Acute metabolic crisis, with a lethal outcome in four patients, was reported for 22/33 clinically symptomatic cases. No clinically symptomatic cases were reported from cohorts with screened by MS-MS. Conclusion: ten potentially treatable organic acidurias and mitochondrial fatty acid transport and oxidations disorders were more common than phenylketonuria with organic acidurias accounting for 28% of the cases detected by newborn screening and 39% of the cases identified on high risk screening. These conditions were related to considerable morbidity and mortality. Considerations for their inclusion in expanded newborn screening programmes might be warranted.Abbreviations
ESPED
Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland (German Paediatric Surveillance Unit)
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MCADD
medium-chain acyl-CoA dehydrogenase deficiency
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MS-MS
tandem mass spectrometry
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mtFATOD
mitochondrial fatty acid transport and oxidation disorders
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NBS
newborn screening
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OA
organic acidurias 相似文献
52.
Anastomotic healing is impaired after intestinal surgery because of ischemia and reperfusion injury (IRI), which can result in intestinal leaks leading to increased mortality. The objective of this study was to determine the effects of transplant IRI and immune mechanisms on intestinal graft anastomotic healing. Orthotopic intestinal transplantations (OIT) were performed in rats. The experimental design consisted of six groups A–F (n = 5/group): A, allogeneic OIT treated with tacrolimus (1mg/kg/day); B, syngeneic OIT treated with tacrolimus; C, syngeneic OIT; D, allogeneic OIT; E, proximal and distal anastomoses performed in nontransplanted animals; F, same as in group E but treated with tacrolimus. Anastomotic bursting pressure (ABP), hydroxyproline content (HPC), and mucosal inflammatory infiltrate (MII) were determined at the anastomotic sites (proximal and distal) and compared between groups. ABP was significantly (p < 0.001) reduced in OIT groups A, B, C, and D compared to control groups E and F at both the proximal and distal anastomotic sites. HPC was 1 g/mg of tissue in groups A, B, C, and D, and 5g/mg of tissue in groups E and F. This demonstrates a significant (p < 0.001) reduction in HPC after OIT. MII was significantly (p < 0.001) increased in OIT groups when compared to nontransplanted control groups. MII was also significantly (p < 0.05) increased in allogeneic OIT groups A and D compared to syngeneic OIT groups B and C. Generally, ABP and HPC were inversely proportional to MII in both nontransplanted control and OIT groups. Reduced anastomotic strength was demonstrated in both syngeneic and allogeneic OIT anastomotic sites irrespective of immunosuppressive therapy, and is probably related to IRI. 相似文献
53.
Treatment of established recurrent hepatitis C in liver-transplant recipients with pegylated interferon-alfa-2b and ribavirin therapy 总被引:13,自引:0,他引:13
Neff GW Montalbano M O'Brien CB Nishida S Safdar K Bejarano PA Khaled AS Ruiz P Slapak-Green G Lee M Nery J De Medina M Tzakis A Schiff ER 《Transplantation》2004,78(9):1303-1307
INTRODUCTION: The management issues of transplant patients with hepatitis C virus (HCV) are complex, and interferon therapy is often ineffective. We present data from a retrospective review in liver-transplant recipients suffering from HCV recurrence that were treated with pegylated alpha-2b interferon and ribavirin. METHODS: A retrospective review of transplant recipients that received combination pegylated alpha-2b interferon (1.5 mcg/kg/wk) and ribavirin (400-600 mg/day) therapy intended for at least 48 weeks. Complications were recorded and included neutropenia (<750 cells), anemia (hemoglobin <8 g) with and without treatment consisting of blood transfusions, erythropoietin, or dose reduction of ribavirin, and depression. The diagnosis of HCV recurrence was determined by an increase in liver chemistries, histopathologic findings with inflammation along with viral recurrence using the COBAS AMPLICOR HCV test. RESULTS: Fifty-seven liver-transplant recipients were included, 29 naive (group 1) to therapy and 28 nonresponders (group 2) to at least 6 months of interferon and ribavirin therapy. Eight (27.6%) patients in group 1 and six (21%) patients in group 2 were HCV nondetectable at the end of 48 weeks of therapy. Ribavirin therapy was decreased in 13 of 29 (45%) for group 1 and 11 of 28 (39%) in group 2. Therapeutic interventions were 4 of 57 (7%) blood transfusions, 23 of 57 (40%) erythropoietin, and 17 of 57 (30%) filgrastim. CONCLUSION: Combination pegylated interferon with ribavirin appears to effective therapy in HCV recurrence and in HCV nonresponsive to interferon and ribavirin. This data reveals the difficulty and caution that must be taken when treating HCV-R liver-transplant recipients with combination pegylated alpha-2b interferon and ribavirin therapy. 相似文献
54.
Little is known about the impact of intestinal transplantation on development of the infant brain. In this study we report four neurodevelopmental studies on children receiving either liver or intestinal/multivisceral transplants. Our preliminary investigation examined the pretransplant status of 27 infants, who were either liver or intestinal/multivisceral candidates, using the Bayley Scales of Infant Development. A second study examined 23 infants after liver or intestinal/multivisceral transplant. A third study included pre- and posttransplant evaluations on 5 multivisceral infant transplants. In the fourth study, 10 children were tested several years after intestinal/multivisceral transplantation. Some children are able to achieve a normal development. However, even several years posttransplant most children can still experience significant cognitive delays. Children receiving a transplant during infancy may also suffer severe motor delays. Infants undergoing intestinal/multivisceral transplantation show significantly more cognitive delays than those undergoing single-organ liver transplantation. In addition, multivisceral transplanted infants are more likely to continue to be severely developmentally delayed at the time of hospital discharge. With improved survival rates for infant transplants, both cognitive and motor development must be evaluated to determine the need for early intervention. In addition, educating families on the importance of compliance with intervention services outside the hospital is essential to maximize long-term neurodevelopmental outcomes for these infants. 相似文献
55.
Campath-1H immunosuppressive therapy reduces incidence and intensity of acute rejection in intestinal and multivisceral transplantation 总被引:3,自引:0,他引:3
Garcia M Weppler D Mittal N Nishida S Kato T Tzakis A Ruiz P 《Transplantation proceedings》2004,36(2):323-324
Campath-1H, an anti-CD52 antibody, is being used at our institution as immunosuppression in multivisceral and intestinal transplantation. We reviewed the pathologic findings of 1696 small bowel allograft biopsies obtained in the first 250 days posttransplant from 78 patients who underwent isolated intestinal or multivisceral transplantation and received induction immunosuppression with Campath (n = 30) or Zenapax (n = 57). We found an overall reduced incidence of acute cellular rejection (ACR) in patients receiving Campath (19.1%) compared with those on Zenapax (32.8%). The majority of Campath patients showed no rejection or was indeterminate for rejection over the period of measurement. The frequencies of mild and moderate ACR were approximately twice and three times more common, respectively, in Zenapax-treated patients. The mean grade of ACR in Campath patients compared with Zenapax patients was significantly lower (P <.01) during the first 6 weeks posttransplant. Thereafter, the grade of rejection in both patient groups showed fluctuation, with Zenapax patients sometimes having lower values (eg, at 2 to 4 months) than Campath patients. Patient and graft survival was not significantly different between the two groups. These data suggest that the incidence of ACR is significantly reduced with Campath during the first 2 months posttransplant, when compared with Zenapax. However, the incidence and intensity of ACR following this initial time period shows vacillation with both types of immunosuppression. 相似文献
56.
57.
A novel micro-cell-mediated lympholytic assay for the evaluation of regulatory cells in human alloreactive CTL responses 总被引:2,自引:0,他引:2
Mathew JM Blomberg B Fuller L Burke GW Ciancio G Kenyon N Ricordi C Tzakis AG Esquenazi V Miller J 《Journal of immunological methods》2003,272(1-2):67-80
Since cell-mediated lympholysis (CML), the most commonly used in vitro experimental cytotoxic method for the evaluation of regulatory cells, requires large numbers of cells that are often the limiting factor, we have developed a new micro-cell-mediated lympholytic (m-CML) assay. Various numbers of responding cells were stimulated with equivalent numbers of allogeneic irradiated stimulator cells in the presence of (fivefold) serial dilutions of regulatory cells. On the 8th day, 4-h 51Cr-release assays were performed by adding 5000 labeled target cells from the corresponding stimulators to the cultures.Even though results that were comparable to the macro- (bulk) CML and MLR modulation experiments were obtained with all the cell combinations tested in the m-CML, the combinations with 50,000 responder cells and stimulating cells and dilutions of 25,000 to 40 modulator (regulatory) cells were found to be the most reproducible for assaying regulatory cell potency in vitro. Similarly, expression of the results as percentage inhibition using percent specific lysis values was the simplest method of calculation. This assay was standardized for the evaluation of the inhibitory activity of a variety of regulatory cells, including long-term cultures of cadaver-donor vertebral body bone marrow cells (vDBMC-L), in vitro generated CD8 positive and CD28 negative suppressor T cells and donor chimeric cells isolated from renal transplant recipients who had been perioperatively infused with donor bone marrow cells (DBMC). The results indicate that the m-CML assay is a sensitive and reliable micromethod with at least 10-fold fewer responders, stimulator and modulator cell numbers needed than macro-CML assays for the evaluation of regulatory cells obtained from a variety of immune systems in vitro. 相似文献
58.
Kobayashi S Kato T Nishida S Buttrago E Maldini G Mittal N Thompson J Tzakis AG 《Pediatric transplantation》2002,6(4):344-347
Necrotizing fasciitis is a rare, subcutaneous infection. It can occur in patients after solid-organ transplantation. We herein report two patients who developed necrotizing fasciitis following combined liver and small intestine transplantation. The first patient experienced this infection 4 yr after transplantation and 1 yr after the closure of the ileostomy. The second patient suffered from necrotizing fasciitis 2 days after the transplant. Both cases were diagnosed on the physical findings, culture of subcutaneous lavage, and the computed tomography findings. The site of entrance of the organism was not clear in either case. Both patients had a fulminant course and died within 1 week from the onset, despite aggressive surgical intervention. Therefore, necrotizing fasciitis has to be recognized as a potential complication of intestinal transplantation. 相似文献
59.
Ruiz P Suarez M Nishida S de la Cruz V Nicolas M Weppler D Khaled A Bejarano P Kato T Mittal N Icardi M Tzakis A 《Transplantation proceedings》2003,35(8):3057-3060
BACKGROUND: Acute rejection of human small bowel allografts is characterized by clinical symptoms combined with characteristic morphologic alterations. The typical geographic distribution of acute rejection in the bowel is involvement of the intestinal parenchyma, which can be transmural, particularly when the rejection is more severe. However, little is known concerning the potential for donor-derived soft tissue adjacent to the bowel to become involved by the host alloimmune response. METHODS: We describe a male patient who, several weeks after combined small bowel and liver transplantation, demonstrated sclerosing mesenteritis with vasculitis and acute rejection of the bowel. RESULTS: The vascular lesions in the mesentery demonstrated increased IgG deposition and the patient developed an alloantibody to the donor. CONCLUSIONS: The changes described herein may represent a novel presentation of acute vascular rejection. 相似文献
60.