全文获取类型
收费全文 | 4476篇 |
免费 | 307篇 |
国内免费 | 20篇 |
专业分类
耳鼻咽喉 | 58篇 |
儿科学 | 109篇 |
妇产科学 | 69篇 |
基础医学 | 771篇 |
口腔科学 | 118篇 |
临床医学 | 397篇 |
内科学 | 887篇 |
皮肤病学 | 111篇 |
神经病学 | 581篇 |
特种医学 | 154篇 |
外科学 | 508篇 |
综合类 | 16篇 |
一般理论 | 2篇 |
预防医学 | 320篇 |
眼科学 | 90篇 |
药学 | 266篇 |
中国医学 | 8篇 |
肿瘤学 | 338篇 |
出版年
2024年 | 4篇 |
2023年 | 36篇 |
2022年 | 63篇 |
2021年 | 138篇 |
2020年 | 75篇 |
2019年 | 107篇 |
2018年 | 109篇 |
2017年 | 114篇 |
2016年 | 149篇 |
2015年 | 180篇 |
2014年 | 219篇 |
2013年 | 240篇 |
2012年 | 396篇 |
2011年 | 364篇 |
2010年 | 230篇 |
2009年 | 197篇 |
2008年 | 296篇 |
2007年 | 321篇 |
2006年 | 336篇 |
2005年 | 256篇 |
2004年 | 237篇 |
2003年 | 183篇 |
2002年 | 157篇 |
2001年 | 61篇 |
2000年 | 45篇 |
1999年 | 48篇 |
1998年 | 44篇 |
1997年 | 25篇 |
1996年 | 15篇 |
1995年 | 15篇 |
1994年 | 6篇 |
1993年 | 12篇 |
1992年 | 11篇 |
1991年 | 14篇 |
1990年 | 11篇 |
1989年 | 12篇 |
1988年 | 12篇 |
1987年 | 7篇 |
1986年 | 12篇 |
1985年 | 9篇 |
1984年 | 9篇 |
1982年 | 3篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 5篇 |
1974年 | 2篇 |
1970年 | 3篇 |
1960年 | 1篇 |
1958年 | 2篇 |
1956年 | 1篇 |
排序方式: 共有4803条查询结果,搜索用时 218 毫秒
1.
2.
Very preterm children are at increased risk of reduced processing speed at 5 years of age,predicted by typical complications of prematurity and prenatal smoking
下载免费PDF全文
![点击此处可从《Acta paediatrica (Oslo, Norway : 1992)》网站下载免费的PDF全文](/ch/ext_images/free.gif)
3.
Jenny U. Johansson Nathaniel S. Woodling Qian Wang Maharshi Panchal Xibin Liang Angel Trueba-Saiz Holden D. Brown Siddhita D. Mhatre Taylor Loui Katrin I. Andreasson 《The Journal of clinical investigation》2015,125(1):350-364
Microglia, the innate immune cells of the CNS, perform critical inflammatory and noninflammatory functions that maintain normal neural function. For example, microglia clear misfolded proteins, elaborate trophic factors, and regulate and terminate toxic inflammation. In Alzheimer’s disease (AD), however, beneficial microglial functions become impaired, accelerating synaptic and neuronal loss. Better understanding of the molecular mechanisms that contribute to microglial dysfunction is an important objective for identifying potential strategies to delay progression to AD. The inflammatory cyclooxygenase/prostaglandin E2 (COX/PGE2) pathway has been implicated in preclinical AD development, both in human epidemiology studies and in transgenic rodent models of AD. Here, we evaluated murine models that recapitulate microglial responses to Aβ peptides and determined that microglia-specific deletion of the gene encoding the PGE2 receptor EP2 restores microglial chemotaxis and Aβ clearance, suppresses toxic inflammation, increases cytoprotective insulin-like growth factor 1 (IGF1) signaling, and prevents synaptic injury and memory deficits. Our findings indicate that EP2 signaling suppresses beneficial microglia functions that falter during AD development and suggest that inhibition of the COX/PGE2/EP2 immune pathway has potential as a strategy to restore healthy microglial function and prevent progression to AD. 相似文献
4.
Molecular determinants of cetuximab efficacy. 总被引:17,自引:0,他引:17
Daniel Vallb?hmer Wu Zhang Michael Gordon Dong Yun Yang Jim Yun Oliver A Press Katrin E Rhodes Andy E Sherrod Syma Iqbal Kathleen D Danenberg Susan Groshen Heinz-Josef Lenz 《Journal of clinical oncology》2005,23(15):3536-3544
PURPOSE: To investigate whether mRNA expression levels of cyclin D1 (CCND1), cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), interleukin 8 (IL-8), and vascular endothelial growth factor (VEGF), all members of the EGFR signaling pathway, are associated with clinical outcome in patients with EGFR-expressing metastatic colorectal cancer (CRC) treated with cetuximab. PATIENTS AND METHODS: Thirty-nine patients with metastatic CRC, refractory to both irinotecan and oxaliplatin, were enrolled on IMCL-0144 and treated with single-agent cetuximab. The intratumoral mRNA levels of CCND1, Cox-2, EGFR, IL-8, and VEGF were assessed from paraffin-embedded tissue samples using laser-capture microdissection and quantitative real-time polymerase chain reaction. RESULTS: There were 21 women and 18 men with a median age of 64 years (range, 35 to 83 years). Higher gene expression levels of VEGF were associated with resistance to cetuximab (P = .038; Kruskal-Wallis test). The combination of low gene expression levels of Cox-2, EGFR, and IL-8 was significantly associated with overall survival (13.5 v 2.3 months; P = .028; log-rank test). Both findings were independent of skin toxicity that was itself significantly correlated to survival. Patients with a lower mRNA amount of EGFR had a longer overall survival compared with patients that had a higher mRNA amount (7.3 v 2.2 months; P = .09; log-rank test). Patients with lower expression of Cox-2 had a significantly higher rate of grade 2 to 3 skin reactions under cetuximab treatment. CONCLUSION: This pilot study suggests that gene expression levels of Cox-2, EGFR, IL-8, and VEGF in patients with metastatic CRC may be useful markers of clinical outcome in single-agent cetuximab treatment. 相似文献
5.
Stefan Ockert Hardy Schumacher Dittmar Böckler Katrin Malcherek Jochen Hansmann Jens Allenberg 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》2007,392(6):725-730
Background and aims Since the introduction of endovascular aortic aneurysm repair (EVAR) for aortic aneurysms, the number of juxtarenal aortic
aneurysms (JRA) has been growing steadily due to selection bias (neck morphology for EVAR). This case-match study compares
the perioperative outcome and midterm results of suprarenally clamped JRA with infrarenal aortic aneurysms (AAA).
Methods From 1997 to 2004, patients who received open surgery with suprarenal clamping for JRA were included in the study and compared
to matched patients with infrarenal clamping (AAA). Measurements analyzed were the in-hospital mortality and morbidity. Midterm
results were obtained through clinical investigation and magnetic resonance angiography imaging.
Results Thirty-five patients (mean age, 68.4 years; 30 male and 5 female) received suprarenal cross-clamping for JRA. The overall
in-hospital mortality for JRA and for the controls (AAA) with elective aortic repair was 4.5% (6.1% JRA; 3% AAA, p = 0.058). The morbidity of JRA was elevated according to the rate of pulmonary complications (p = 0.021) and the need for re-operation (p = 0.019). The mean follow-up time was 2.3 years (range, 8–96 months). At follow-up, 28 patients (80%) from the JRA group
and 29 patients from the AAA group (82.9%) were alive.
Conclusion Open aortic surgery for JRA with the need for suprarenal cross-clamping shows a slightly elevated in-hospital mortality rate
without statistical significance and equal midterm mortality results in comparison with infrarenally clamped aortic aneurysms. 相似文献
6.
7.
Anemia has a high prevalence in patients with cancer. Its frequency and severity depend on tumor type, tumor stage, duration of disease, and treatment status. The etiology of cancer-related anemia is multifactorial and includes myelotoxicity of treatment, bone marrow infiltration, impaired erythropoietin production, blood loss, and the anemia of chronic disease. Anemia affects health-related quality of life (QOL) and may impact on tolerance or even outcome of anticancer therapy. Despite its high prevalence and impact on QOL, anemia is often under-recognized and under-treated. Treatment should correct etiologic factors, whenever possible. Symptomatic treatments are red blood cell transfusions and administration of erythropoietic growth factors. Transfusions result in rapid improvement of anemia-related symptoms but are usually only given to patients with moderate to severe anemia. Administration of epoetins (epoetin alfa, epoetin beta) or darbepoetin alfa increases hemoglobin levels, reduces the need for blood transfusions, and improves QOL in patients with cancer-related anemia. Trials determining the exact association of anemia with both response to chemo(radio)therapy and survival are ongoing. Physicians should be aware of the clinical relevance of and treatment options for anemia in cancer patients. 相似文献
8.
Birgit Herting MD Bettina Beuthien‐Baumann MD Katrin Pöttrich PhD Markus Donix MD Antje Triemer PhD Johannes B. Lampe MD Rüdiger von Kummer MD Karl Herholz MD Heinz Reichmann MD Vjera A. Holthoff MD 《Movement disorders》2007,22(4):490-497
Depressive symptoms are common in patients with neurodegenerative disorders. Imaging studies suggest that a disruption of frontal-subcortical pathways may underlie depression associated with basal ganglia disease. This pilot study tested the hypothesis that frontal dysfunction contributes to depression associated with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Depressed patients with MSA (n = 11), PSP (n = 9), and age-matched controls (n = 25) underwent measures of cerebral glucose metabolism applying positron emission tomography with (18)F-fluorodeoxyglucose. Regional metabolism in the patient groups was compared to the normal subjects using the voxel-based statistical parametric mapping. Depressive symptom severity (Hamilton Depression Rating) and degree of locomotor disability (Hoehn & Yahr) were assessed in the patient groups. The association between prefrontal metabolism and the occurrence of depressive symptoms and the degree of locomotor disability was investigated. When compared to controls, MSA patients revealed significant metabolic decreases in bilateral frontal, parietal, and cerebellar cortex and in the left putamen. In PSP patients, significant hypometabolism was demonstrated in bilateral frontal cortex, right thalamus, and midbrain. Depression severity but not the patients' functional condition was significantly associated with dorsolateral prefrontal glucose metabolism in both patient groups. The findings of this pilot study support the hypothesis that depressive symptoms in MSA and PSP are associated with prefrontal dysfunction. 相似文献
9.
N. M. van Schoor D. L. Knol C. A. W. Glas R. W. J. G. Ostelo A. Leplège C. Cooper O. Johnell P. Lips 《Osteoporosis international》2006,17(4):543-551
Introduction Vertebral deformities are a common consequence of osteoporosis and are known to decrease quality of life. The Qualeffo–41
is a quality-of-life questionnaire especially developed for measuring quality of life in patients with vertebral deformities.
It consists of 41 questions arranged in five domains: pain, physical function, social function, general health perception,
and mental function. The objectives of this study were: (1) to develop a shorter version of the Qualeffo–41 by removing redundant
questions; and (2) to investigate the scale characteristics, reliability, and validity of this shorter version.
Methods The study was performed using data from the Qualeffo validation study and the Multiple Outcomes of Raloxifene Evaluation (MORE)
study. The analyses were performed in patients with vertebral deformities (n=579). Factor analysis on polychoric correlations and an item response theory (IRT) model, i.e., the generalized partial credit
model (GPCM), were used to create a shorter version of Qualeffo–41. Using GPCM, scoring weights were computed for all items.
Results Three items were removed from the data set because of too many missing values. Factor analysis identified three instead of
five domains: (1) pain, (2) physical function, and (3) mental function. Five items had factor loadings <0.4 and were not included
in the GPCM. After excluding several items, the domains pain (four items), physical function (18 items), and mental function
(nine items) showed a good, reasonable, and excellent fit, respectively. This indicates that the mental function domain and
the pain domain are more unidimensional than the physical function domain. All three domains showed a very high correlation
(r ≥0.95) with the corresponding domains of the Qualeffo–41.
Conclusions Qualeffo–31 was developed, consisting of three domains with a reasonable to excellent fit to the GPCM. Although the fit to
the GPCM supports the construct validity of the Qualeffo–31, validation in a new study should be performed before using it
in practice. 相似文献
10.
T Gloudemans I Pospiech L T Van Der Ven C J Lips H Schneid W Den Otter J S Sussenbach 《Cancer research》1992,52(23):6516-6521
Previously we have shown that expression of the insulin-like growth factor II (IGF-II) gene in 36 normal smooth muscle tissues (myometria) and 26 benign smooth muscle tumors (leiomyomas) was detectable by Northern blot analysis but that the RNA levels were low. In 9 of 20 malignant smooth muscle tumors (leiomyosarcomas) IGF-II gene expression was also low or absent, while in 11 of 20 the IGF-II gene was abundantly expressed. In 32 of these tissues we have now studied the DNA methylation state of the IGF-II gene. For the analysis of overall methylation of the gene the restriction endonucleases HpaII and MspI were used. In normal smooth muscle and in leiomyomas the IGF-II gene appeared to be methylated. In leiomyosarcomas with low IGF-II gene expression the DNA was partly demethylated. In leiomyosarcomas with abundant IGF-II gene expression overall methylation of the DNA tended to be low. In addition, we have studied the methylation state of one particular CpG site in the IGF-II gene with the restriction endonuclease AvaII. The results of the latter analysis confirm the analysis with HpaII and MspI. In conclusion, in malignant smooth muscle tumors the data indicate an inverse correlation between CpG methylation and expression of the IGF-II gene. 相似文献