全文获取类型
收费全文 | 455篇 |
免费 | 27篇 |
国内免费 | 7篇 |
专业分类
儿科学 | 5篇 |
妇产科学 | 5篇 |
基础医学 | 115篇 |
口腔科学 | 14篇 |
临床医学 | 38篇 |
内科学 | 128篇 |
皮肤病学 | 4篇 |
神经病学 | 43篇 |
特种医学 | 9篇 |
外科学 | 49篇 |
综合类 | 3篇 |
预防医学 | 21篇 |
眼科学 | 1篇 |
药学 | 32篇 |
中国医学 | 2篇 |
肿瘤学 | 20篇 |
出版年
2023年 | 7篇 |
2022年 | 7篇 |
2021年 | 15篇 |
2020年 | 9篇 |
2019年 | 7篇 |
2018年 | 14篇 |
2017年 | 10篇 |
2016年 | 12篇 |
2015年 | 14篇 |
2014年 | 26篇 |
2013年 | 25篇 |
2012年 | 28篇 |
2011年 | 32篇 |
2010年 | 15篇 |
2009年 | 14篇 |
2008年 | 27篇 |
2007年 | 27篇 |
2006年 | 29篇 |
2005年 | 28篇 |
2004年 | 17篇 |
2003年 | 20篇 |
2002年 | 13篇 |
2001年 | 3篇 |
2000年 | 5篇 |
1999年 | 6篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 5篇 |
1993年 | 1篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1986年 | 7篇 |
1985年 | 7篇 |
1984年 | 7篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 8篇 |
1976年 | 3篇 |
1975年 | 5篇 |
1974年 | 4篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1970年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有489条查询结果,搜索用时 0 毫秒
1.
Immunoglobulin Gene Rearrangement in Plasma Cell Dyscrasias: Detection of Small Clonal Cell Populations in Peripheral Blood and Bone Marrow 总被引:1,自引:0,他引:1
Falko Fend Katharina Weyrer Johannes Drach Andrea Schwaiger Florian Umlauft Kurt Grü newald 《Leukemia & lymphoma》1993,10(3):223-229
The bone marrow (BM) and peripheral blood (PB) samples of 71 patients with plasma cell dyscrasias were analysed by the Southern blot technique for the presence of clonal immunoglobulin (Ig) gene rearrangements. 53% of BM samples examined were archival material such as air dried BM slides or frozen trephine biopsies. The results were related to bone marrow plasmacytosis as determined by cytology and flow cytometry, and other clinical parameters. Clonal Ig gene rearrangements were found in BM samples of 45 (83%) of 54 MM patients and in 3 of 6 patients with monoclonal gammopathy of unknown significance (MGUS). Clonal cell populations in the PB were detected in 11 (30%) of 37 examined MM patients, but in none of the patients with MGUS or solitary plasmacytoma of bone. PB involvement was associated with progressive disease. Circulating monoclonal cells were significantly associated with higher M-protein levels (p 0.05). Thus, circulating clonal precursor cells are encountered more frequently in active MM. 相似文献
2.
3.
Mantle Cell Lymphomas Lack Expression of p27kip1, a Cyclin-Dependent Kinase Inhibitor 总被引:5,自引:0,他引:5 下载免费PDF全文
Leticia Quintanilla-Martinez Catherine Thieblemont Falko Fend Shimareet Kumar Magda Pinyol Elias Campo Elaine S. Jaffe Mark Raffeld 《The American journal of pathology》1998,153(1):175-182
p27Kip1 is a cyclin-dependent kinase inhibitor that regulates the decision to enter S phase or withdraw from the cell cycle. In resting cells, the level of p27Kip1 provides an inhibitory threshold above which G1 cyclin D/E/cyclin-dependent kinases accumulate before activation; however, in cycling cells, p27Kip1 protein is sequestered by high levels of active cyclin D/cyclin-dependent kinase 4 complexes. As a group, the cyclin-dependent kinase inhibitors have been proposed to act as tumor suppressor genes, and several members have been implicated in the pathogenesis of a variety of human cancers. We examined p27Kip1 expression in 116 non-Hodgkin’s lymphomas including 50 cases of MCL (40 typical and 10 blastic variants), 21 follicular lymphomas, 20 diffuse large B-cell lymphomas, 16 chronic lymphocytic leukemias, 8 marginal zone B-cell lymphomas, and 1 splenic marginal zone lymphoma, and correlated its expression with that of the proliferation marker Ki67 (MiB1) and with p53. p27Kip1gene structure was analyzed by Southern blot in the group of MCLs. In all cases of non-Hodgkin’s lymphoma other than MCL, p27Kip1 expression was inversely related to the proliferation index as measured by Ki67. In contrast, in typical MCL, p27Kip1 expression was negative in 35 of 40 (88%) cases, irrespective of the proliferative rate (median 15%; range 2 to 90%). Paradoxically, in the blastic variant of MCL, 8 of 10 (80%) cases showed expression of p27Kip1, despite a high proliferation rate (median 60%; range 32 to 100%). However, the staining in most of the cases was less intense than in the reactive T lymphocytes. Deletions of p27Kip1gene were not found in any of the 25 cases examined. p53 expression was found in 15 of 50 cases of MCL: 7 of 10 (70%) in the blastic variant and 8 of 40 (20%) in the typical MCL (70% vs. 20%, P < 0.0045). These results demonstrate that MCLs, in contrast to other non-Hodgkin’s lymphomas and normal lymphoid tissue, fail to correlate p27Kip1 expression with the proliferation rate. This peculiar uncoupling of p27Kip1 protein expression from the proliferation rate may be related to the high levels of cyclin D1 expressed in MCL and is likely to have profound effects on cell cycle regulation and contribute to the pathogenesis of MCL. 相似文献
4.
Armando Gamboa-Dominguez Claudia Dominguez-Fonseca Leticia Quintanilla-Martinez Edgardo Reyes-Gutierrez Dan Green Arturo Angeles-Angeles Raymonde Busch Christine Hermannst?dter J?rg N?hrig Karl-Friedrich Becker Ingrid Becker Heinz H?fler Falko Fend Birgit Luber 《Modern pathology》2004,17(5):579-587
The aim of the study was to determine epidermal growth factor receptor (EGFR) expression in gastric adenocarcinoma by standardized immunohistochemistry and to correlate EGFR expression with clinical features and patient survival. EGFR expression was investigated in paraffin sections of resection specimens of 89 gastric carcinomas from Mexican Mestizo patients using standardized immunohistochemistry with antigen retrieval (Dako EGFRpharmDx assay detection system). Membrane staining of EGFR was evaluated in the neoplastic cells and graded using a semiquantitative score (0-3+). Of the 89 carcinomas examined, staining of neoplastic cells was weak in 17 (19.1%, score 1+), moderate in 16 (18.0%, score 2+), and strong in nine cases (10.1%, score 3+). EGFR reactivity was heterogeneous, frequently showing completely negative up to 3+ positive areas within an individual tumor. EGFR reactivity score correlated with distant metastases (P=0.002) and clinical stage (P=0.033). EGFR score 0/1+ was significantly associated with an increase in patient survival when compared to score 2+/3+ (P=0.0006). In a multivariate analysis, EGFR positive cells in muscularis or subserosa (P=0.004), distant metastases (P=0.016) and residual disease (P=0.039) were significantly correlated with decreased survival. The prognosis was associated with the EGFR reactivity score (P=0.003), distant metastases (P=0.0001) and residual disease (P=0.012) in a univariate analysis. EGFR reactivity in neoplastic cells is an independent prognostic factor in gastric adenocarcinoma. The relevance of the heterogeneity in EGFR expression with regard to tumor progression, metastasis and anti-EGFR therapy needs to be studied. 相似文献
5.
Genetic ablation of FLRT3 reveals a novel morphogenetic function for the anterior visceral endoderm in suppressing mesoderm differentiation 总被引:1,自引:0,他引:1
Joaquim Egea Christian Erlacher Eloi Montanez Ingo Burtscher Satoru Yamagishi Martin Heß Falko Hampel Rodrigo Sanchez Maria Teresa Rodriguez-Manzaneque Michael R. Bsl Reinhard Fssler Heiko Lickert Rüdiger Klein 《Genes & development》2008,22(23):3349-3362
During early mouse development, the anterior visceral endoderm (AVE) secretes inhibitor and activator signals that are essential for establishing the anterior–posterior (AP) axis of the embryo and for restricting mesoderm formation to the posterior epiblast in the primitive streak (PS) region. Here we show that AVE cells have an additional morphogenetic function. These cells express the transmembrane protein FLRT3. Genetic ablation of FLRT3 did not affect the signaling functions of the AVE according to the normal expression pattern of Nodal and Wnt and the establishment of a proper AP patterning in the epiblast. However, FLRT3−/− embryos showed a highly disorganized basement membrane (BM) in the AVE region. Subsequently, adjacent anterior epiblast cells displayed an epithelial-to-mesenchymal transition (EMT)-like process characterized by the loss of cell polarity, cell ingression, and the up-regulation of the EMT and the mesodermal marker genes Eomes, Brachyury/T, and FGF8. These results suggest that the AVE acts as a morphogenetic boundary to prevent EMT and mesoderm induction in the anterior epiblast by maintaining the integrity of the BM. We propose that this novel function cooperates with the signaling activities of the AVE to restrict EMT and mesoderm induction to the posterior epiblast. 相似文献
6.
7.
Sina Schwarzkopf Adalbert Krawczyk Dietmar Knop Hannes Klump Andreas Heinold Falko M. Heinemann Laura Thümmler Christian Temme Marianne Breyer Oliver Witzke Ulf Dittmer Veronika Lenz Peter A. Horn Monika Lindemann 《Emerging infectious diseases》2021,27(1):122
We investigated immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a group of convalescent, potential blood donors in Germany who had PCR-confirmed SARS-CoV-2 infection. Sixty days after onset of symptoms, 13/78 (17%) study participants had borderline or negative results to an ELISA detecting IgG against the S1 protein of SARS-CoV-2. We analyzed participants with PCR-confirmed infection who had strong antibody responses (ratio >3) as positive controls and participants without symptoms of SARS-CoV-2 infection and without household contact with infected patients as negative controls. Using interferon-γ ELISpot, we observed that 78% of PCR-positive volunteers with undetectable antibodies showed T cell immunity against SARS-CoV-2. We observed a similar frequency (80%) of T-cell immunity in convalescent donors with strong antibody responses but did not detect immunity in negative controls. We concluded that, in convalescent patients with undetectable SARS-CoV-2 IgG, immunity may be mediated through T cells. 相似文献
8.
Christian A. Skrabal Amir Khosravi Bernd Westphal Gustav Steinhoff 《Scandinavian cardiovascular journal : SCJ》2013,47(4):224-229
Objectives. In this study, the immuno- and neuroprotective effect of a novel cardiopulmonary bypass coating was investigated. Design. Thirty nine patients scheduled for elective coronary artery bypass grafting were randomly assigned to either PMEA-coated (n?=?19) or non-coated CPB circuits (n?=?20). Pericardial suction blood was separated and retransfused only if needed at the end of operation. Neurocognitive functions were examined preoperatively and 7–10 days postoperatively using a standard neuropsychological test battery. Assuming an inflammatory etiology, the most cogent inflammatory markers were perioperatively analyzed. Results. Postoperatively, patients of the PMEA-coated group performed better in Go/NoGo and Mini-Mental-test than patients of the non-coated group (p?<?0.04). Other neurocognitive testing did not reveal significant differences between the groups. Although most inflammatory parameters showed a significant intraindividual increase during or shortly after CPB, there was no difference in inflammatory alteration between the groups. Conclusions. PMEA-coating of cardiopulmonary bypass surfaces revealed some minor benefits in preservation of neurocognitive functions after surgery. The immediate inflammatory response remained mostly unaffected. Suction blood separation may additionally contribute to proper postoperative outcome. 相似文献
9.
Akbar Dastjerdi John Carr Richard J. Ellis Falko Steinbach Susanna Williamson 《Emerging infectious diseases》2015,21(12):2235-2237
An outbreak of porcine epidemic diarrhea occurred in the summer of 2014 in Ukraine, severely affecting piglets <10 days of age; the mortality rate approached 100%. Full genome sequencing showed the virus to be closely related to strains reported from North America, showing a sequence identity of up to 99.8%. 相似文献
10.
Low sodium/high potassium diet for prevention of hypertension: probable mechanisms of action 总被引:2,自引:0,他引:2
20 normotensive subjects (10 with a family history of hypertension) were investigated as to whether moderate salt restriction and/or a high potassium intake had a beneficial effect on blood pressure regulation and prevention of hypertension. In all subjects a moderate reduction of salt intake from 200 to 50 mmol/day over 2 weeks reduced the rise in blood pressure induced by various doses of noradrenaline (0.1, 0.2, and 0.4 microgram/kg/min). Furthermore, of 20 subjects 12 (8 with a family history of hypertension) responded to salt restriction with a fall in systolic or diastolic blood pressure of at least 5 mm Hg. There were no significant differences in plasma renin, aldosterone, vasopressin, and catecholamine levels between responders (salt-sensitive subjects) and non-responders, but salt-sensitive subjects had a mean baseline diastolic blood pressure which was higher than that of salt-insensitive subjects by 13 mm Hg (77.3+/-3.26 vs. 64.6+/-2.06, p less than 0.001). A high potassium intake reduced diastolic blood pressure by at least 5 mm Hg in 10 out of 20 subjects, of the 10 7 had a family history of hypertension and 9 responded to salt restriction. A high potassium intake also improved compliance with a low salt regimen, promoted sodium loss, prevented the rise in plasma catecholamines induced by a low salt diet, and increased the sensitivity of the baroreceptor reflex. These four effects occurred in the group as a whole and were probably the means by which a high potassium intake reduced blood pressure. In all subjects 2 weeks of a combined low sodium/high potassium intake reduced blood pressure rises induced by mental stress or noradrenaline infusion by 10 mm Hg. The results of this study suggest that moderate salt restriction combined with a high potassium intake helps to prevent hypertension, that salt-sensitive subjects exist, and that these individuals would profit most. 相似文献