全文获取类型
收费全文 | 1787篇 |
免费 | 142篇 |
国内免费 | 1篇 |
出版年
2023年 | 4篇 |
2022年 | 25篇 |
2021年 | 37篇 |
2020年 | 13篇 |
2019年 | 23篇 |
2018年 | 33篇 |
2017年 | 25篇 |
2016年 | 58篇 |
2015年 | 102篇 |
2014年 | 114篇 |
2013年 | 111篇 |
2012年 | 174篇 |
2011年 | 133篇 |
2010年 | 94篇 |
2009年 | 90篇 |
2008年 | 122篇 |
2007年 | 111篇 |
2006年 | 91篇 |
2005年 | 84篇 |
2004年 | 98篇 |
2003年 | 87篇 |
2002年 | 83篇 |
2001年 | 18篇 |
2000年 | 17篇 |
1999年 | 21篇 |
1998年 | 27篇 |
1997年 | 15篇 |
1996年 | 19篇 |
1995年 | 8篇 |
1994年 | 11篇 |
1993年 | 10篇 |
1992年 | 7篇 |
1991年 | 2篇 |
1990年 | 7篇 |
1989年 | 5篇 |
1988年 | 3篇 |
1987年 | 5篇 |
1986年 | 6篇 |
1985年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 4篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1973年 | 2篇 |
1925年 | 1篇 |
排序方式: 共有1930条查询结果,搜索用时 15 毫秒
111.
Marsche G Hammer A Oskolkova O Kozarsky KF Sattler W Malle E 《The Journal of biological chemistry》2002,277(35):32172-32179
Hypochlorous acid/hypochlorite (HOCl/OCl(-)), a potent oxidant generated in vivo by the myeloperoxidase-H(2)O(2)-chloride system of activated phagocytes, alters the physiological properties of high density lipoprotein (HDL) by generating a proatherogenic lipoprotein particle. On endothelial cells lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) and scavenger receptor class B, type I (SR-BI), act in concert by mediating the holoparticle of and selective cholesteryl ester uptake from HOCl-HDL. We therefore investigated the ligand specificity of HOCl-HDL to SR-BI-overexpressing Chinese hamster ovary cells. Binding of HOCl-HDL was saturable, and the degree of HOCl modification was the determining factor for increased binding affinity to SR-BI. Competition experiments further confirmed that HOCl-HDL binds with increased affinity to the same or overlapping domain(s) of SR-BI as does native HDL. Furthermore, SR-BI-mediated selective HDL-cholesteryl ester association as well as time- and concentration-dependent cholesterol efflux from SR-BI overexpressing Chinese hamster ovary cells were, depending on the degree of HOCl modification of HDL, markedly impaired. The most significant findings of this study were that the presence of very low concentrations of HOCl-HDL severely impaired SR-BI-mediated bidirectional cholesterol flux mediated by native HDL. The colocalization of immunoreactive HOCl-modified epitopes with apolipoprotein A-I along with deposits of lipids in serial sections of human atheroma shown here indicates that the myeloperoxidase-H(2)O(2)-halide system contributes to oxidative damage of HDL in vivo. 相似文献
112.
The availability of safe and reliable, banked tissues in India has enabled the use of human bone allografts as a viable alternative to autografts in reconstructive surgery. Lyophilised, irradiated bone grafts were used in 2 cases of rhinoplasty, a case of hemifacial atrophy, and as a chin implant.In the patient with revision rhinoplasty the rib graft was resorbed. The patient with hemifacial atrophy developed seroma and infection in the zygomatic and infraorbital area and the rib graft had to be removed. The graft from the same rib that was placed over the mandible was retained well and incorporated completely. The iliac crest cortico-cancellous grafts did well in the second case of augmentation rhinoplasty and in the augmentation of chin.The primary objective of reconstructive surgery in the treatment of burns, non-healing wounds and pressure sores is to remove the dead tissue and restore the continuity of the skin without delay. Lyophilised, irradiated, human amnion is a temporary biological dressing conveniently available off-the-shelf. It was used in twenty four patients with burns, eight patients with bedsores and six patients with non-healing ulcers mainly on the foot. The total surface areas of burns sustained were from 2% to 40%. The burns ranged from second degree to deep third degree burns. Amnion was not used in patients with infected third degree burns.The amnion provided good biological cover in all the patients. It was easy to handle and apply, and provided pain relief. The duration of healing varied depending on the extent and depth of the wound and the amount of exudate. The superficial bedsores healed with a single application of amnion. Reduced exudate, healthy granulation tissue and enhanced epithelisation were observed following application of amnion. 相似文献
113.
One of the great strengths of the Framingham Heart Study data, provided for the Genetic Analysis Workshop 13, is the long-term survey of phenotypic data. We used this unique data to create new phenotypes representing the pattern of longitudinal change of the provided phenotypes, especially systolic blood pressure and body weight. We performed a linear regression of body weight and systolic blood pressure on age and took the slopes as new phenotypes for quantitative trait linkage analysis using the SOLAR package. There was no evidence for heritability of systolic blood pressure change. Heritability was estimated as 0.15 for adult life "body weight change", measured as the regression slope, and "body weight gain" (including only individuals with a positive regression slope), and as 0.22 for body weight "change up to 50" (regression slope of weight on age up to an age of 50). With multipoint analysis, two regions on the long arm of chromosome 8 showed the highest LOD scores of 1.6 at 152 cM for "body weight change" and of >1.9 around location 102 cM for "body weight gain" and "change up to 50". The latter two LOD scores almost reach the threshold for suggestive linkage. We conclude that the chromosome 8 region may harbor a gene acting on long-term body weight regulation, thereby contributing to the development of the metabolic syndrome. 相似文献
114.
Bj?rn?Audun?Ris?y Truls?Raastad Jostein?Hallén Knut?T?Lappeg?rd Kjersti?B?verfjord Astrid?Kravdal Else?Marie?Siebke Haakon?B?BenestadEmail author 《BMC physiology》2003,3(1):14
Background
During infections, polymorphonuclear neutrophilic granulocytes (PMN) are mobilized from their bone marrow stores, travel with blood to the affected tissue, and kill invading microbes there. The signal(s) from the inflammatory site to the marrow are unknown, even though a number of humoral factors that can mobilize PMN, are well known. We have employed a standardized, non-infectious human model to elucidate relevant PMN mobilizers. Well-trained athletes performed a 60-min strenuous strength workout of leg muscles. Blood samples were drawn before, during and just after exercise, and then repeatedly during the following day. Cortisol, GH, ACTH, complement factors, high-sensitive CRP (muCRP), IL-6, G-CSF, IL-8 (CXCL8) and MIP-1β (CCL4) were measured in blood samples. PMN chemotaxins in test plasma was assessed with a micropore membrane technique. 相似文献115.
Heterogeneity of microvascular endothelial cells isolated from human term placenta and macrovascular umbilical vein endothelial cells 总被引:6,自引:0,他引:6
Lang I Pabst MA Hiden U Blaschitz A Dohr G Hahn T Desoye G 《European journal of cell biology》2003,82(4):163-173
The present study compares some phenotypic and physiologic characteristics of microvascular and macrovascular endothelial cells from within one human organ. To this end microvascular endothelial cells from human full-term placenta (PLEC) were isolated using a new method and compared with macrovascular human umbilical vein endothelial cells (HUVEC) and an SV40-transformed placental venous endothelial cell line (HPEC-A2). PLEC were isolated by enzymatic perfusion of small placental vessels, purified on a density gradient and cultured subsequently. Histological sections of the enzyme-treated vessels showed a selective removal of the endothelial lining in the perfused placental cotyledons. The endothelial identity of the cells was confirmed by staining with the endothelial markers anti-von Willebrand factor, Ulex europaeus lectin and anti-QBEND10. The cells internalized acetylated low-density lipoprotein and did not show immunoreactivity with markers for macrophages, smooth muscle cells and fibroblasts. The spindle-shaped PLEC grew in swirling patterns similar to that described for venous placental endothelial cells. However, scanning electron microscopic examination clearly showed that PLEC remained elongated at the confluent state, in contrast to the more polygonal phenotype of HPEC-A2 and HUVEC that were studied in parallel. The amount of vasoactive substances (endothelin-1,2, thromboxane, angiotensin II, prostacyclin) released into the culture medium and the proliferative response to cytokines was more similar to human dermal microvessels (MIEC) derived from non-fetal tissue than to HUVEC. Potent mitogens such as vascular endothelial growth factors (VEGF121, VEGF165) and basic fibroblast growth factor (FGF-2) induced proliferation of all endothelial cell types. Placental growth factors PIGF-1 and PIGF-2 effectively stimulated cell proliferation on PLEC (142 +/- 7% and 173 +/- 10%) and MIEC (160 +/- 20% and 143 +/- 28%) in contrast to HUVEC (9 +/- 8% and 15 +/- 20%) and HPEC-A2 (15 +/- 7% and 24 +/- 6%) after 48 h incubation time under serum-free conditions. These data support evidence for (1) the microvascular identity of the isolated PLEC described in this study, and (2) the phenotypic and physiologic heterogeneity of micro- and macrovascular endothelial cells within one human organ. 相似文献
116.
Bibliography
Bibliography 相似文献117.
118.
Virus Attenuation after Deletion of the Cytomegalovirus Fc Receptor Gene Is Not due to Antibody Control 总被引:2,自引:0,他引:2 下载免费PDF全文
Irena Crnkovi-Mertens Martin Messerle Irena Miloti Uwe Szepan Natalija Ku
i Astrid Krmpoti Stipan Jonji Ulrich H. Koszinowski 《Journal of virology》1998,72(2):1377-1382
The murine cytomegalovirus (MCMV) fcr-1 gene codes for a glycoprotein located at the surface of infected cells which strongly binds the Fc fragment of murine immunoglobulin G. To determine the biological significance of the fcr-1 gene during viral infection, we constructed MCMV fcr-1 deletion mutants and revertants. The fcr-1 gene was disrupted by insertion of the Escherichia coli lacZ gene. In another mutant, the marker gene was also deleted, by recombinase cre. As expected for its hypothetical role in immunoevasion, the infection of mice with fcr-1 deletion mutants resulted in significantly restricted replication in comparison with wild-type MCMV and revertant virus. In mutant mice lacking antibodies, however, the fcr-1 deletion mutants also replicated poorly. This demonstrated that the cell surface-expressed viral glycoprotein with FcR activity strongly modulates the virus-host interaction but that this biological function is not caused by the immunoglobulin binding property. 相似文献
119.
Karina Preu?el Astrid Milde-Busch Patrick Schmich Matthias Wetzstein Klaus Stark Dirk Werber 《PloS one》2015,10(11)
Non-pregnancy associated (N-PA) listeriosis, caused by Listeria monocytogenes, is a rare but severe disease, and is predominantly food-borne. Most cases appear sporadic and their infection vehicle remains unknown. Incidence has increased since 2008 in Germany. We aimed to identify underlying conditions and foods associated with sporadic N-PA listeriosis in Germany. We performed a nationwide case-control study from March 2012-December 2013. Cases were sporadic N-PA listeriosis patients notified to public health. Control subjects were age (40–65 years, 66–75 years, ≥76 years) frequency-matched persons from a nationwide random telephone sample. A structured questionnaire collected information on underlying diseases, therapies and >60 food items. We conducted multivariable logistic regression analysis, adjusting for host factors identified by causal diagram theory, and calculated population attributable fractions. We enrolled 109 cases and 1982 controls. Cases’ median age was 69 years, 55% were male, 44% received immunosuppressive therapy within 3 months prior to illness onset; a further 28% had at least one immunocompromising disease. In multivariable analysis, immunosuppressive therapy (OR 8.8, 95%CI 4.9–15.6), immunocompromising disease (OR 2.7; 95%CI 1.4–5.2), gastric acid suppression (OR 3.0; 95%CI 1.4–6.3), the consumption of cold cooked sausages (OR 2.6; 95%CI 1.6–4.4), the preferred consumption of packaged cheese (OR 2.1; 95%CI 1.3–3.5) and pre-sliced cheese (OR 2.2; 95%CI 1.3–3.7) were significantly associated with N-PA listeriosis. These foods accounted for 59% of all cases. Typical high risk foods, e.g. cold seafood, certain types of cheeses, tended to be negatively associated with disease. In conclusion, immunosuppressive therapy and frequently consumed ready-to-eat foods are the main risk factors for sporadic N-PA listeriosis in Germany. To reduce their risk, immunocompromised persons should consume the identified foods well before the ‘use-by’ date. The microbiological criteria for Listeria monocytogenes in ready-to-eat foods may insufficiently protect persons who are markedly immunocompromised. 相似文献
120.
Esther Wehrle Astrid Liedert Aline Heilmann Tim Wehner Ronny Bindl Lena Fischer Melanie Haffner-Luntzer Franz Jakob Thorsten Schinke Michael Amling Anita Ignatius 《Disease models & mechanisms》2015,8(1):93-104
Fracture healing is impaired in aged and osteoporotic individuals. Because adequate mechanical stimuli are able to increase bone formation, one therapeutical approach to treat poorly healing fractures could be the application of whole-body vibration, including low-magnitude high-frequency vibration (LMHFV). We investigated the effects of LMHFV on fracture healing in aged osteoporotic mice. Female C57BL/6NCrl mice (n=96) were either ovariectomised (OVX) or sham operated (non-OVX) at age 41 weeks. When aged to 49 weeks, all mice received a femur osteotomy that was stabilised using an external fixator. The mice received whole-body vibrations (20 minutes/day) with 0.3 g peak-to-peak acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, micro-computed tomography (μCT), histology and gene expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with significantly reduced flexural rigidity (−81%) and bone formation (−80%) in the callus. Gene expression analyses demonstrated increased oestrogen receptor β (ERβ, encoded by Esr2) and Sost expression in the callus of the vibrated animals, but decreased β-catenin, suggesting that ERβ might mediate these negative effects through inhibition of osteoanabolic Wnt/β-catenin signalling. In contrast, in OVX mice, LMHFV significantly improved callus properties, with increased flexural rigidity (+1398%) and bone formation (+637%), which could be abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered in a 90-day-release pellet). On a molecular level, we found an upregulation of ERα in the callus of the vibrated OVX mice, whereas ERβ was unaffected, indicating that ERα might mediate the osteoanabolic response. Our results indicate a major role for oestrogen in the mechanostimulation of fracture healing and imply that LMHFV might only be safe and effective in confined target populations.KEY WORDS: Whole-body vibration, LMHFV, Fracture healing, Oestrogen receptor signalling, Wnt signalling 相似文献