全文获取类型
收费全文 | 209篇 |
免费 | 21篇 |
国内免费 | 3篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 12篇 |
妇产科学 | 8篇 |
基础医学 | 27篇 |
口腔科学 | 2篇 |
临床医学 | 44篇 |
内科学 | 37篇 |
皮肤病学 | 5篇 |
神经病学 | 7篇 |
特种医学 | 17篇 |
外科学 | 10篇 |
综合类 | 17篇 |
预防医学 | 14篇 |
药学 | 19篇 |
肿瘤学 | 13篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 3篇 |
2020年 | 2篇 |
2019年 | 1篇 |
2018年 | 3篇 |
2017年 | 3篇 |
2016年 | 3篇 |
2015年 | 7篇 |
2014年 | 5篇 |
2013年 | 11篇 |
2012年 | 8篇 |
2011年 | 6篇 |
2010年 | 5篇 |
2009年 | 12篇 |
2008年 | 6篇 |
2007年 | 3篇 |
2006年 | 3篇 |
2005年 | 9篇 |
2004年 | 5篇 |
2003年 | 13篇 |
2002年 | 9篇 |
2001年 | 3篇 |
2000年 | 7篇 |
1999年 | 4篇 |
1998年 | 19篇 |
1997年 | 15篇 |
1996年 | 13篇 |
1995年 | 6篇 |
1994年 | 9篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1982年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1971年 | 1篇 |
排序方式: 共有233条查询结果,搜索用时 15 毫秒
1.
Disturbed homeostasis of lung intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 during sepsis
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Laudes IJ Guo RF Riedemann NC Speyer C Craig R Sarma JV Ward PA 《The American journal of pathology》2004,164(4):1435-1445
Cecal ligation and puncture (CLP)-induced sepsis in mice was associated with perturbations in vascular adhesion molecules. In CLP mice, lung vascular binding of (125)I-monoclonal antibodies to intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 revealed sharp increases in binding of anti-ICAM-1 and significantly reduced binding of anti-VCAM-1. In whole lung homogenates, intense ICAM-1 up-regulation was found (both in mRNA and in protein levels) during sepsis, whereas very little increase in VCAM-1 could be measured although some increased mRNA was found. During CLP soluble VCAM-1 (sVCAM-1) and soluble ICAM-1 (sICAM-1) appeared in the serum. When mouse dermal microvascular endothelial cells (MDMECs) were incubated with serum from CLP mice, constitutive endothelial VCAM-1 fell in association with the appearance of sVCAM-1 in the supernatant fluids. Under the same conditions, ICAM-1 cell content increased in MDMECs. When MDMECs were evaluated for leukocyte adhesion, exposure to CLP serum caused increased adhesion of neutrophils and decreased adhesion of macrophages and T cells. The progressive build-up in lung myeloperoxidase after CLP was ICAM-1-dependent and independent of VLA-4 and VCAM-1. These data suggest that sepsis disturbs endothelial homeostasis, greatly favoring neutrophil adhesion in the lung microvasculature, thereby putting the lung at increased risk of injury. 相似文献
2.
Arbour NC; Zlotogora J; Knowlton RG; Merin S; Rosenmann A; Kanis AB; Rokhlina T; Stone EM; Sheffield VC 《Human molecular genetics》1997,6(5):689-694
Achromatopsia is an autosomal recessive disease of the retina,
characterized clinically by an inability to distinguish colors, impaired
visual acuity, nystagmus and photophobia. A genome-wide search for linkage
was performed using an inbred Jewish kindred from Iran. To facilitate the
genome-wide search, we utilized a DNA pooling strategy which takes
advantage of the likelihood that the disease in this inbred kindred is
inherited by all affected individuals from a common founder. Equal molar
amounts of DNA from all affected individuals were pooled and used as the
PCR template for short tandem repeat polymorphic markers (STRPs). Pooled
DNA from unaffected members of the kindred was used as a control. A
reduction in the number of alleles in the affected versus control pool was
observed at several loci. Upon genotyping of individual family members,
significant linkage was established between the disease phenotype and
markers localized on chromosome 2. The highest LOD score observed was 5.4
(theta = 0). When four additional small unrelated families were genotyped,
the combined peak LOD score was 8.2. Analysis of recombinant chromosomes
revealed that the disease gene lies within a 30 cM interval which spans the
centromere. Additional fine-mapping studies identified a region of
homozygosity in all affected individuals, narrowing the region to 14 cM. A
candidate gene for achromatopsia was excluded from this disease interval by
radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an
essential first step in the identification of the disease-causing gene.
相似文献
3.
4.
5.
Javier Arístegui Vytautas Usonis Hoosen Coovadia Stella Riedemann Khin Maung Win Salvacion Gatchalian Hans L Bock 《International journal of infectious diseases》2003,7(2):143-151
BACKGROUND: Vaccines are important weapons in the fight against infectious diseases. The World Health Organization (WHO) Expanded Program on Immunization (EPI) has been extended to include recommendations for hepatitis B and Haemophilus influenzae type b (Hib) vaccinations. The WHO has recommended that combined vaccines be used where possible, to reduce the logistic costs of vaccine delivery. This paper reviews the efficacy, safety and cost-effectiveness of Tritanrix-HB/Hib, the only commercially available combined diphtheria, tetanus, whole cell pertussis, hepatitis B and conjugated Hib vaccine. METHODS: The immunogenicity and reactogenicity results of five published clinical trials involving Tritanrix-HB/Hib in a variety of immunization schedules and countries were reviewed. Based on these data and cost-effectiveness studies, an assessment of its suitability for use in national immunization programs was made. RESULTS: Tritanrix-HB/Hib has shown excellent immunogenicity in clinical trials using a variety of schedules, with no reduced immunogenicity observed for any of the components of the combined vaccine. It has similar reactogenicity to DTPw vaccines alone. Pharmacoeconomic analyses have shown combined DTP-HB/Hib vaccines to be cost-effective compared to separate vaccines. CONCLUSIONS: Replacement of DTPw vaccination by Tritanrix-HB/Hib can be done without modifying the existing national immunization programs. This should facilitate widespread coverage of hepatitis B and Hib vaccinations and their rapid incorporation into the EPI. 相似文献
6.
In vivo expression of the B7 costimulatory molecule by subsets of antigen-presenting cells and the malignant cells of Hodgkin's disease 总被引:10,自引:0,他引:10
Munro JM; Freedman AS; Aster JC; Gribben JG; Lee NC; Rhynhart KK; Banchereau J; Nadler LM 《Blood》1994,83(3):793-798
The B-lymphocyte/accessory-cell activation antigen B7 (BB1) has been shown in vitro to stimulate T-lymphocyte proliferation and cytokine production via CD28 present on the latter cells. In this study, benign lymphoid tissues, lymphomas, and extralymphoid inflammatory sites were examined immunohistochemically using anti-B7 and other relevant monoclonal antibodies. B7 was expressed by benign transformed germinal center B cells, as it was by B cells of follicular lymphomas. B7 was also expressed by a subpopulation (a mean of 31% to 65%) of macrophages and dendritic cells in a variety of lymphoid tissues. It was present in abundance on all macrophages constituting sarcoid granulomas in lymph nodes. In extralymphoid inflammation, 17% to 35% of macrophages expressed B7 only weakly. Cases of Hodgkin's disease showed expression of B7 by the majority of Reed-Sternberg cells or malignant mononuclear variants, a phenomenon that potentially contributes to the lymphocytic accumulation that is a feature of this condition. CD28+ T cells were seen in all areas where T cells were present. B7+ and CD28+ cells colocalized in, for example, lymphoid follicles, lymph node paracortex, sarcoid granulomas, and Hodgkin's disease tissue, indicating a potential for cellular interaction via these molecules at these sites. 相似文献
7.
Stella Riedemann Germán Reinhardt Jaime Jara Richard Rios María Soledad Wenzel Paul Willems Hans L Bock 《International journal of infectious diseases》2002,6(3):215-222
OBJECTIVES: To determine the immunogenicity and reactogenicity of a combined DTPw-HBV/Hib vaccine, in comparison with DTPw-HBV and Hib vaccines given as separate concomitant injections. METHODS: In an open, randomized study, healthy infants were injected with either DTPw-HBV/Hib vaccine or separate DTPw-HBV and Hib vaccines at 2, 4 and 6 months of age, with a booster at 18 months. RESULTS: Both vaccination regimens were immunogenic, with seropositivity rates of 100% after the booster vaccination for all vaccine components. Even as early as 2 months after the second dose of the primary vaccination, most patients had seroprotective antibody titers, the proportion of seropositive subjects approaching 100% for tetanus, hepatitis B, and Hib. Post-primary and post-booster geometric mean titers (GMTs) were well above seroprotective thresholds for each vaccine antigen in both groups, with no clinically relevant differences in the groups. The separate and combined administrations showed comparable reactogenicity profiles, and neither showed a significant increase in reactogenicity with successive doses. CONCLUSIONS: The results of this study support the combination of Hib and DTPw-HBV vaccination in routine infant immunization at 2, 4 and 6 months of age with a booster at 18 months. Maximum benefit is obtained from compliance with the full course, but substantial benefit is likely to be achieved even in partially compliant patients, provided they receive at least two doses. Furthermore, these results demonstrate the tolerability of a fourth (booster) administration, where the addition of the Hib vaccine to DTPw-HBV did not lead to an increase in the overall reactogenicity. 相似文献
8.
Alexander P. J. Vlaar Endry H. T. Lim Sanne de Bruin Simon Rückinger Korinna Pilz Matthijs C. Brouwer RenFeng Guo Leo
M. A. Heunks Matthias H. Busch Pieter van Paassen Niels
C. Riedemann Diederik van de Beek 《CTS Clinical and Translational Science》2022,15(4):854
Recently, we reported the phase II portion of the adaptive phase II/III PANAMO trial exploring potential benefit and safety of selectively blocking C5a with the monoclonal antibody vilobelimab (IFX‐1) in patients with severe coronavirus disease 2019 (COVID‐19). The potent anaphylatoxin C5a attracts neutrophils and monocytes to the infection site, causes tissue damage by oxidative radical formation and enzyme releases, and leads to activation of the coagulation system. Results demonstrated that C5a inhibition with vilobelimab was safe and secondary outcomes appeared in favor of vilobelimab. We now report the pharmacokinetic/pharmacodynamic (PK/PD) analysis of the phase II study. Between March 31 and April 24, 2020, 30 patients with severe COVID‐19 pneumonia confirmed by real‐time polymerase chain reaction were randomly assigned 1:1 to receive vilobelimab plus best supportive care or best supportive care only. Samples for measurement of vilobelimab, C3a and C5a blood concentrations were taken. Vilobelimab predose (trough) drug concentrations in plasma ranged from 84,846 to 248,592 ng/ml (571 to 1674 nM) with a geometric mean of 151,702 ng/ml (1022 nM) on day 2 and from 80,060 to 200,746 ng/ml (539 to 1352 nM) with a geometric mean of 139,503 ng/ml (939 nM) on day 8. After the first vilobelimab infusion, C5a concentrations were suppressed in the vilobelimab group (median 39.70 ng/ml 4.8 nM, IQR 33.20–45.55) as compared to the control group (median 158.53 ng/ml 19.1 nM, IQR 60.03–200.89, p = 0.0006). The suppression was maintained on day 8 (p = 0.001). The current PK/PD analysis shows that vilobelimab efficiently inhibits C5a in patients with severe COVID‐19. Study Highlights
- WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
- WHAT QUESTION DID THIS STUDY ADDRESS?
- WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
- HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
9.
10.
Ward PA Riedemann NC Guo RF Huber-Lang M Sarma JV Zetoune FS 《Scandinavian journal of infectious diseases》2003,35(9):601-603
Using the cecal ligation/puncture (CLP) model of sepsis in rodents, evidence was obtained for excessive activation of the complement system, which leads to nearly total loss of innate immune protective functions of blood neutrophils. These defects are associated with profound defects in chemotaxis, respiratory burst (H2O2 production) and phagocytosis. The molecular mechanisms of these defects are linked to the complement activation product C5a. In CLP rats and mice, the C5a receptor (C5aR) is widely up-regulated in organs, in part owing to the production of interleukin-6 (IL-6). The up-regulation of C5aR in the thymus is linked to C5a-dependent induction of apoptosis in thymocytes, as revealed by caspase activation, increased binding of C5a and DNA laddering. Such events in thymocytes are prevented if rats first are treated with anti-C5a or with anti-C5aR at the time of CLP. Treatment of CLP rats and mice with anti-C5a, anti-IL-6 or anti-C5aR dramatically improves survival rates after CLP, indicating a linkage between C5a and C5aR in the harmful outcomes of sepsis in rodents. Studies are underway in humans with sepsis to determine whether similar mechanisms are in play. 相似文献