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101.
Soufi M Schoppet M Sattler AM Herzum M Maisch B Hofbauer LC Schaefer JR 《The Journal of clinical endocrinology and metabolism》2004,89(8):3764-3768
Osteoprotegerin (OPG) antagonizes receptor activator of nuclear factor-kappaB ligand (RANKL), the principal regulator of osteoclasts. Of note, OPG-deficient mice display osteoporosis and arterial calcification. Recently, OPG gene polymorphisms have been associated with osteoporosis and early predictors of cardiovascular disease. In this study, we examined OPG gene polymorphisms in 468 men who had absence of coronary artery disease (CAD) or single-, double-, or triple-vessel disease on coronary angiography. Denaturing gradient gel electrophoresis followed by DNA sequencing revealed nucleotide substitutions 149 T-->C, 163 A-->G, 209 G-->A, 245 T-->G, 950 T-->C (all promoter), 1181 G-->C (exon 1), and 6890 A-->C (intron 4), respectively. Although single polymorphisms were not associated with CAD, linkage of polymorphisms 950 and 1181 revealed that haplotypes were overrepresented in men with CAD (chi(2) = 17.05; P = 0.03) with an increased risk of CAD in carriers of genotypes 950 TC/1181 GC and 950 CC/1181 CC (odds ratio, 1.67; 95% confidence interval, 1.02-2.72; P = 0.04). Furthermore, serum OPG levels were correlated with the presence of a C allele at position 950 (P = 0.02). In summary, linkage of genetic variations of the OPG gene at positions 950 and 1181 may confer an increased risk of CAD in Caucasian men. 相似文献
102.
G Allmendinger E Blaich F Hofg?rtner H Lorenz E Schmid 《Zeitschrift für Gastroenterologie》1984,22(2):62-65
35 out of 57 patients with gastric carcinoma presented with a so called "target" pattern. In cases with distal cancer the more advanced cases with endoscopic types Borrmann III/IV showed this sign more frequently than less advanced forms, i.e. suspected early cancer, Borrmann I or Borrmann II. On the other hand in endoscopically advanced cancers Borrmann III/IV a thickening of the gastric wall was more frequent in distal than in proximal localization of carcinoma. The presence of target sign in abdominal ultrasound did, statistically, not influence gastric resection. Other findings, which were observed exclusively in gastric cancer type Borrmann III/IV, like infiltration to the surrounding (pancreas, liver), liver metastasis, and/or ascites, were decisive. Additional sonography of the abdomen is, therefore, a valuable preoperative diagnostic procedure in gastric cancer beside upper GI endoscopy and biopsy. 相似文献
103.
Coronary collateral perfusion in patients with coronary artery disease: effect of metoprolol. 总被引:2,自引:0,他引:2
Michael Billinger Lorenz Raeber Christian Seiler Stephan Windecker Bernhard Meier Otto M Hess 《European heart journal》2004,25(7):565-570
BACKGROUND: The use of ultrathin Doppler angioplasty guidewires has made it possible to measure collateral flow quantitatively. Pharmacologic interventions have been shown to influence collateral flow and, thus, to affect myocardial ischaemia. METHODS: Twenty-five patients with coronary artery disease undergoing PTCA were included in the present analysis. Coronary flow velocities were measured in the ipsilateral (n = 25) and contralateral (n = 6; two Doppler wires) vessels during PTCA with and without i.v. adenosine (140 microg/kg.min) before and 3 min after 5 mg metoprolol i.v., respectively. The ipsilateral Doppler wire was positioned distal to the stenosis, whereas the distal end of the contralateral wire was in an angiographically normal vessel. The flow signals of the ipsilateral wire were used to calculate the collateral flow index (CFI). CFI was defined as the ratio of flow velocity during balloon inflation divided by resting flow. RESULTS: Heart rate and mean aortic pressure decreased slightly (ns) after i.v. metoprolol. The collateral flow index was 0.25+/-0.12 (one fourth of the resting coronary flow) during the first PTCA and 0.27+/-0.14 (ns versus first PTCA) during the second PTCA, but decreased with metoprolol to 0.16+/-0.08 (p<0.0001 vs. baseline) during the third PTCA. CONCLUSIONS: Coronary collateral flow increased slightly but not significantly during maximal vasodilatation with adenosine but decreased in 23 of 25 patients after i.v. metoprolol. Thus, there is a reduction in coronary collateral flow with metoprolol, probably due to an increase in coronary collateral resistance or a reduction in oxygen demand. 相似文献
104.
105.
Venigalla RK Tretter T Krienke S Max R Eckstein V Blank N Fiehn C Ho AD Lorenz HM 《Arthritis and rheumatism》2008,58(7):2120-2130
OBJECTIVE: CD4+,CD25high regulatory T (Treg) cells play a crucial role in the maintenance of self tolerance and prevention of organ-specific autoimmunity. The presence of many in vivo-preactivated CD4+,CD25++ T cells in patients with systemic lupus erythematosus (SLE) poses a difficulty in discriminating CD25++ activated T cells from CD25high Treg cells. To overcome this problem, we analyzed the phenotype and function of CD4+,CD25high,CD127(-/low) natural Treg (nTreg) cells isolated from the peripheral blood of patients with SLE. METHODS: CD4+,CD25high,CD127(-/low) nTreg cells and CD4+,CD25- responder T (Tresp) cells from patients with SLE and normal donors were separated by fluorescence-activated cell sorting. Cell proliferation was quantified by 3H-thymidine incorporation, and immunophenotyping of the cells was done using FACScan. RESULTS: Comparable percentages of CD4+,CD25high,FoxP3+ T cells were observed in patients with SLE and normal donors. Proliferation of SLE nTreg cells sorted into the subset CD4+,CD25high,CD127(-/low) was significantly decreased compared with that of SLE nTreg cells sorted into the subset CD4+,CD25high (mean +/- SEM 2,223 +/- 351 counts per minute versus 9,104 +/- 1,720 cpm, respectively), while in normal donors, these values were 802 +/- 177 cpm and 2,028 +/- 548 cpm, respectively, confirming that effector cell contamination was reduced. Notably, the suppressive activity of nTreg cells was intact in all groups. However, CD4+,CD25- Tresp cells isolated from patients with active SLE were significantly less sensitive than those from patients with inactive SLE to the suppressive function of autologous or normal donor CD4+,CD25high,CD127(-/low) nTreg cells. Furthermore, a significant inverse correlation was observed between the extent of T cell regulation in suppressor assays and the level of lupus disease activity. CONCLUSION: This study is the first to show that, in human SLE, impaired sensitivity of Tresp cells to the suppressive effects of a comparably functional, highly purified nTreg cell population leads to a defective suppression of T cell proliferation in active SLE. Studies aiming to define the mechanisms leading to Tresp cell resistance might help in the development of highly specific, alternative immunotherapeutic tools for the control of systemic autoimmune diseases such as SLE. 相似文献
106.
OBJECTIVE: To evaluate bone metabolism in patients with ankylosing spondylitis (AS) and test the hypothesis that osteoprotegerin (OPG) serum concentrations are correlated with the severity of bone loss as assessed by bone mineral density (BMD) and biochemical markers of bone turnover. Osteoporosis occurs frequently in patients with AS and OPG represents a soluble decoy receptor that neutralizes receptor activator of nuclear factor-kB ligand (RANKL), an essential cytokine for osteoclast function. METHODS: Clinical data, radiographs of the spine, BMD of lumbar spine and the femur, biochemical markers of bone turnover, and serum levels of OPG were evaluated in 264 patients with AS (72% men) and 240 age-matched healthy controls (76% men). RESULTS: OPG serum levels were significantly lower in patients with AS compared to controls (1.84 +/- 1.15 vs 3.54 +/- 2.18 pmol/l, p < 0.001), and in contrast to controls, were not positively correlated with age. In addition, BMD of the hip and the femoral neck were significantly lower in patients with AS than in controls. There were positive correlations in patients with AS between BMD of the femoral neck and free testosterone serum levels in men and free estradiol serum levels in women, respectively. Patients with AS and osteoporosis had higher biochemical markers of bone resorption and inflammatory activity. CONCLUSION: Bone loss in patients with AS is associated with low sex steroid hormone serum levels, high biochemical markers of bone resorption and inflammatory activity, low OPG serum levels, and lack of compensatory age-related increase of OPG serum levels. 相似文献
107.
Drew D. DAngelo Yoshihito Sakata John N. Lorenz Gregory P. Boivin Richard A. Walsh Stephen B. Liggett Gerald W. Dorn II 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(15):8121-8126
The critical cell signals that trigger cardiac hypertrophy and regulate the transition to heart failure are not known. To determine the role of Gαq-mediated signaling pathways in these events, transgenic mice were constructed that overexpressed wild-type Gαq in the heart using the α-myosin heavy chain promoter. Two-fold overexpression of Gαq showed no detectable effects, whereas 4-fold overexpression resulted in increased heart weight and myocyte size along with marked increases in atrial naturietic factor (≈55-fold), β-myosin heavy chain (≈8-fold), and α-skeletal actin (≈8-fold) expression, and decreased (≈3-fold) β-adrenergic receptor-stimulated adenylyl cyclase activity. All of these signals have been considered markers of hypertrophy or failure in other experimental systems or human heart failure. Echocardiography and in vivo cardiac hemodynamic studies indeed revealed impaired intrinsic contractility manifested as decreased fractional shortening (19 ± 2% vs. 41 ± 3%), dP/dt max, a negative force–frequency response, an altered Starling relationship, and blunted contractile responses to the β-adrenergic agonist dobutamine. At higher levels of Gαq overexpression, frank cardiac decompensation occurred in 3 of 6 animals with development of biventricular failure, pulmonary congestion, and death. The element within the pathway that appeared to be critical for these events was activation of protein kinase C. Interestingly, mitogen-activated protein kinase, which is postulated by some to be important in the hypertrophy program, was not activated. The Gαq overexpressor exhibits a biochemical and physiologic phenotype resembling both the compensated and decompensated phases of human cardiac hypertrophy and suggests a common mechanism for their pathogenesis. 相似文献
108.
The PCBP1 gene encoding poly(rc) binding protein i is recurrently mutated in Burkitt lymphoma
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Rabea Wagener Sietse M. Aukema Matthias Schlesner Andrea Haake Birgit Burkhardt Alexander Claviez Hans G. Drexler Michael Hummel Markus Kreuz Markus Loeffler Maciej Rosolowski Cristina Lpez Peter Mller Julia Richter Marius Rohde Matthew J. Betts Robert B. Russell Stephan H. Bernhart Steve Hoffmann Philip Rosenstiel Markus Schilhabel Monika Szczepanowski Lorenz Trümper Wolfram Klapper Reiner Siebert 《Genes, chromosomes & cancer》2015,54(9):555-564
The genetic hallmark of Burkitt lymphoma is the translocation t(8;14)(q24;q32), or one of its light chain variants, resulting in IG‐MYC juxtaposition. However, these translocations alone are insufficient to drive lymphomagenesis, which requires additional genetic changes for malignant transformation. Recent studies of Burkitt lymphoma using next generation sequencing approaches have identified various recurrently mutated genes including ID3, TCF3, CCND3, and TP53. Here, by using similar approaches, we show that PCBP1 is a recurrently mutated gene in Burkitt lymphoma. By whole‐genome sequencing, we identified somatic mutations in PCBP1 in 3/17 (18%) Burkitt lymphomas. We confirmed the recurrence of PCBP1 mutations by Sanger sequencing in an independent validation cohort, finding mutations in 3/28 (11%) Burkitt lymphomas and in 6/16 (38%) Burkitt lymphoma cell lines. PCBP1 is an intron‐less gene encoding the 356 amino acid poly(rC) binding protein 1, which contains three K‐Homology (KH) domains and two nuclear localization signals. The mutations predominantly (10/12, 83%) affect the KH III domain, either by complete domain loss or amino acid changes. Thus, these changes are predicted to alter the various functions of PCBP1, including nuclear trafficking and pre‐mRNA splicing. Remarkably, all six primary Burkitt lymphomas with a PCBP1 mutation expressed MUM1/IRF4, which is otherwise detected in around 20–40% of Burkitt lymphomas. We conclude that PCBP1 mutations are recurrent in Burkitt lymphomas and might contribute, in cooperation with other mutations, to its pathogenesis. © 2015 Wiley Periodicals, Inc. 相似文献
109.
Hypoxia‐inducible factor‐3α promotes angiogenic activity of pulmonary endothelial cells by repressing the expression of the VE‐cadherin gene
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110.
Sara Huber Roland Lang Markus Steiner Lorenz Aglas Fatima Ferreira Michael Wallner Thomas Hawranek Gabriele Gadermaier 《Clinical and translational allergy》2018,8(1):39