全文获取类型
收费全文 | 4027篇 |
免费 | 298篇 |
国内免费 | 39篇 |
专业分类
耳鼻咽喉 | 65篇 |
儿科学 | 121篇 |
妇产科学 | 141篇 |
基础医学 | 473篇 |
口腔科学 | 101篇 |
临床医学 | 510篇 |
内科学 | 753篇 |
皮肤病学 | 82篇 |
神经病学 | 213篇 |
特种医学 | 258篇 |
外国民族医学 | 1篇 |
外科学 | 668篇 |
综合类 | 166篇 |
一般理论 | 1篇 |
预防医学 | 229篇 |
眼科学 | 90篇 |
药学 | 228篇 |
中国医学 | 5篇 |
肿瘤学 | 259篇 |
出版年
2021年 | 48篇 |
2020年 | 31篇 |
2019年 | 52篇 |
2018年 | 71篇 |
2017年 | 45篇 |
2016年 | 56篇 |
2015年 | 62篇 |
2014年 | 111篇 |
2013年 | 133篇 |
2012年 | 185篇 |
2011年 | 172篇 |
2010年 | 125篇 |
2009年 | 129篇 |
2008年 | 193篇 |
2007年 | 171篇 |
2006年 | 199篇 |
2005年 | 157篇 |
2004年 | 130篇 |
2003年 | 160篇 |
2002年 | 174篇 |
2001年 | 117篇 |
2000年 | 146篇 |
1999年 | 109篇 |
1998年 | 65篇 |
1997年 | 51篇 |
1996年 | 45篇 |
1995年 | 51篇 |
1994年 | 35篇 |
1993年 | 33篇 |
1992年 | 75篇 |
1991年 | 79篇 |
1990年 | 79篇 |
1989年 | 93篇 |
1988年 | 83篇 |
1987年 | 86篇 |
1986年 | 78篇 |
1985年 | 70篇 |
1984年 | 57篇 |
1983年 | 68篇 |
1982年 | 42篇 |
1981年 | 47篇 |
1980年 | 42篇 |
1979年 | 52篇 |
1978年 | 28篇 |
1977年 | 26篇 |
1975年 | 23篇 |
1974年 | 40篇 |
1973年 | 25篇 |
1972年 | 32篇 |
1969年 | 27篇 |
排序方式: 共有4364条查询结果,搜索用时 187 毫秒
121.
N. Gerber D. H. Ilson A. J. Wu Y. Y. Janjigian D. P. Kelsen J. Zheng Z. Zhang M. S. Bains N. Rizk V. W. Rusch K. A. Goodman 《Diseases of the esophagus》2014,27(3):235-241
This study looks at toxicity and survival data when chemoradiation (CRT) is delivered using intensity‐modulated radiation therapy (IMRT) after induction chemotherapy. Forty‐one patients with esophageal adenocarcinoma treated with IMRT from March 2007 to May 2009 at Memorial Sloan‐Kettering Cancer Center were analyzed. All patients received induction chemotherapy prior to CRT. Thirty‐nine percent (n = 16) of patients underwent surgical resection less than 4 months after completing CRT. Patients were predominantly male (78%), with a median age of 68 years (range 32–85 years). The majority of acute treatment‐related toxicity was hematologic or gastrointestinal, with 17% of patients having grade 3+ hematologic toxicity and 12% of patients having grade 3+ gastrointestinal toxicity. Only two patients developed grade 2–3 pneumonitis (5%) and 5 patients experienced post‐operative pulmonary complications (29%). Eight patients (20%) required a treatment break. With a median follow up of 41 months for surviving patients, 2‐year overall survival was 61%, and the cumulative incidences of local failure (LF) and distant metastases were 40% and 51%, respectively. This rate of LF was reduced to 13% in patients who underwent surgical resection. Surgery and younger age were significant predictors of decreased time to LF on univariate analysis. Induction chemotherapy followed by CRT using IMRT in the treatment of esophageal cancer is well tolerated and is not associated with an elevated risk of postoperative pulmonary complications. The use of IMRT may allow for integration of more intensified systemic therapy or radiation dose escalation for esophageal adenocarcinoma, ultimately improving outcomes for patients with this aggressive disease. 相似文献
122.
D. M. Di Michele C. Gibb J. M. Lefkowitz Q. Ni L. M. Gerber A. Ganguly 《Haemophilia》2014,20(2):e136-e143
Haemophilia A and B are rare X‐lined hemorrhagic disorders that typically affect men. Women are usually asymptomatic carriers, but may be symptomatic and, rarely, also express severe (factor VIII (FVIII) or factor IX (FIX) <0.01 U mL?1) or moderately severe (FVIII/FIX 0.01–0.05 U mL?1) phenotypes. However, data on clinical manifestations, genotype and the psychosocial ramifications of illness in severely affected females remain anecdotal. A national multi‐centre retrospective study was conducted to collect a comprehensive data set on affected US girls and women, and to compare clinical observations to previously published information on haemophilic males of comparable severity and mildly affected haemophilic females . Twenty‐two severe/moderate haemophilia A/B subjects were characterized with respect to clinical manifestations and disease complications; genetic determinants of phenotypic severity; and health‐related quality of life (HR‐QoL). Clinical data were compared as previously indicated. Female patients were older than male patients at diagnosis, but similarly experienced joint haemorrhage, disease‐ and treatment‐related complications and access to treatment. Gynaecological and obstetrical bleeding was unexpectedly infrequent. F8 or F9 mutations, accompanied by extremely skewed X‐chromosome inactivation pattern (XIP), were primary determinants of severity. HR‐QoL was diminished by arthropathy and viral infection. Using systematic case verification of participants in a national surveillance registry, this study elucidated the genetics, clinical phenotype and quality of life issues in female patients with severe/moderate haemophilia. An ongoing international case‐controlled study will further evaluate these observations. Novel mechanistic questions are raised about the relationship between XIP and both age and tissue‐specific FVIII and FIX expression. 相似文献
123.
Mallika Ghosh Claire Gerber M. Mamunur Rahman Kaitlyn M. Vernier Flavia E. Pereira Jaganathan Subramani Leslie A. Caromile Linda H. Shapiro 《Immunology》2014,142(4):636-647
CD13/Aminopeptidase N is a transmembrane metalloproteinase that is expressed in many tissues where it regulates various cellular functions. In inflammation, CD13 is expressed on myeloid cells, is up‐regulated on endothelial cells at sites of inflammation and mediates monocyte/endothelial adhesion by homotypic interactions. In animal models the lack of CD13 alters the profiles of infiltrating inflammatory cells at sites of ischaemic injury. Here, we found that CD13 expression is enriched specifically on the pro‐inflammatory subset of monocytes, suggesting that CD13 may regulate trafficking and function of specific subsets of immune cells. To further dissect the mechanisms regulating CD13‐dependent trafficking we used the murine model of thioglycollate‐induced sterile peritonitis. Peritoneal monocytes, macrophages and dendritic cells were significantly decreased in inflammatory exudates from global CD13KO animals when compared with wild‐type controls. Furthermore, adoptive transfer of wild‐type and CD13KO primary myeloid cells, or wild‐type myeloid cells pre‐treated with CD13‐blocking antibodies into thioglycollate‐challenged wild‐type recipients demonstrated fewer CD13KO or treated cells in the lavage, suggesting that CD13 expression confers a competitive advantage in trafficking. Similarly, both wild‐type and CD13KO cells were reduced in infiltrates in CD13KO recipients, confirming that both monocytic and endothelial CD13 contribute to trafficking. Finally, murine monocyte cell lines expressing mouse/human chimeric CD13 molecules demonstrated that the C‐terminal domain of the protein mediates CD13 adhesion. Therefore, this work verifies that the altered inflammatory trafficking in CD13KO mice is the result of aberrant myeloid cell subset trafficking and further defines the molecular mechanisms underlying this regulation. 相似文献
124.
Jillian Price Carey Escheik Ali Weinstein Patrice Winter Lynn Gerber Zobair Younossi 《Journal of clinical hypertension (Greenwich, Conn.)》2020,22(10):1915
People with Hepatitis C (HCV) and non‐alcoholic fatty liver disease (NAFLD) in the United States follow national trends toward a sedentary lifestyle and are increasingly at risk for hypertension. The intent of this study was to identify potential correlates of exercise tolerance in people with two types of chronic liver disease (CLD)‐NAFLD and HCV. Measures included cardiac output, oxygen consumption and stroke volume, blood pressure, distance walked in 6 minutes, clinical laboratory tests, and medications influencing the autonomic nervous system, patient self‐reports of activity, fatigue, and health‐related quality of life (HRQL). A total of 67 patients completed the 6‐minute walk test [45.1% Female, Age 51.7 ± 8.0 years, Body Mass Index 32.8 ± 5.9, 60% HCV]. At baseline, 70% had either diastolic (DBP) or systolic blood pressure outside normal range. Performance and cardiorespiratory measures correlated strongly with one another, but not with activity. Patients with abnormal DBP reported significantly lower maximum activity (MAS; r = −.254, P = .041, CI = −0.51 to −0.010; MAS 70.6 vs 82.5), significantly higher DBP post‐6‐minute walk test (r = .524, P = .0001, CI = 0.287‐0.762) and significantly lower overall HRQL items related to physical domains (r = .273, P = .029, CI = −0.518 to −0.029). Mental‐domain HRQL and depression measures did not correlate significantly with blood pressure. This study reports a significant correlation between both pre‐hypertensive and hypertensive DBP, poor physical‐domain self‐reports, HRQL, and performance in CLD patients. 相似文献
125.
Oliver M. Theusinger Stephanie L. Kind Burkhardt Seifert lain Borgeat Christian Gerber Donat R. Spahn 《Trasfusione del sangue》2014,12(2):195-203
Background
The aim of this study was to investigate the impact of the introduction of a Patient Blood Management (PBM) programme in elective orthopaedic surgery on immediate pre-operative anaemia, red blood cell (RBC) mass loss, and transfusion.Materials and methods
Orthopaedic operations (hip, n=3,062; knee, n=2,953; and spine, n=2,856) performed between 2008 and 2011 were analysed. Period 1 (2008), was before the introduction of the PBM programme and period 2 (2009 to 2011) the time after its introduction. Immediate pre-operative anaemia, RBC mass loss, and transfusion rates in the two periods were compared.Results
In hip surgery, the percentage of patients with immediate pre-operative anaemia decreased from 17.6% to 12.9% (p<0.001) and RBC mass loss was unchanged, being 626±434 vs 635±450 mL (p=0.974). Transfusion rate was significantly reduced from 21.8% to 15.7% (p<0.001). The number of RBC units transfused remained unchanged (p=0.761). In knee surgery the prevalence of immediate pre-operative anaemia decreased from 15.5% to 7.8% (p<0.001) and RBC mass loss reduced from 573±355 to 476±365 mL (p<0.001). The transfusion rate dropped from 19.3% to 4.9% (p<0.001). RBC transfusions decreased from 0.53±1.27 to 0.16±0.90 units (p<0.001). In spine surgery the prevalence of immediate pre-operative anaemia remained unchanged (p=0.113), RBC mass loss dropped from 551±421 to 404±337 mL (p<0.001), the transfusion rate was reduced from 18.6 to 8.6% (p<0.001) and RBC transfusions decreased from 0.66±1.80 to 0.22±0.89 units (p=0.008).Discussion
Detection and treatment of pre-operative anaemia, meticulous surgical technique, optimal surgical blood-saving techniques, and standardised transfusion triggers in the context of PBM programme resulted in a lower incidence of immediate pre-operative anaemia, reduction in RBC mass loss, and a lower transfusion rate. 相似文献126.
Gerber JM Smith BD Ngwang B Zhang H Vala MS Morsberger L Galkin S Collector MI Perkins B Levis MJ Griffin CA Sharkis SJ Borowitz MJ Karp JE Jones RJ 《Blood》2012,119(15):3571-3577
Relapse of acute myeloid leukemia (AML) is thought to reflect the failure of current therapies to adequately target leukemia stem cells (LSCs), the rare, resistant cells presumed responsible for maintenance of the leukemia and typically enriched in the CD34(+)CD38(-) cell population. Despite the considerable research on LSCs over the past 2 decades, the clinical significance of these cells remains uncertain. However, if clinically relevant, it is expected that LSCs would be enriched in minimal residual disease and predictive of relapse. CD34(+) subpopulations from AML patients were analyzed by flow cytometry throughout treatment. Sorted cell populations were analyzed by fluorescence in situ hybridization for leukemia-specific cytogenetic abnormalities (when present) and by transplantation into immunodeficient mice to determine self-renewal capacity. Intermediate (int) levels of aldehyde dehydrogenase (ALDH) activity reliably distinguished leukemic CD34(+)CD38(-) cells capable of engrafting immunodeficient mice from residual normal hematopoietic stem cells that exhibited relatively higher ALDH activity. Minimal residual disease detected during complete remission was enriched for the CD34(+)CD38(-)ALDH(int) leukemic cells, and the presence of these cells after therapy highly correlated with subsequent clinical relapse. ALDH activity appears to distinguish normal from leukemic CD34(+)CD38(-) cells and identifies those AML cells associated with relapse. 相似文献
127.
We here investigate the occurrence of fluoride intake-associated alterations in patients with hematologic disease on triazol antifungal medication. Clinical, laboratory, and radiology data of overall 43 patients with hematologic malignancies taking voriconazole (n = 20), posaconazole (n = 8), and itraconazole (n = 4), and a hematologic patient control group (n = 11) are described. Bone pain and radiologic evidence of periostitis were exclusively observed in patients receiving long-term voriconazole. Cessation of treatment led to clinical improvement in all cases. In line with clinical evidence, fluoride serum concentration was elevated in patients receiving voriconazole (median, 156.5 μg/L; interquartile range, 96.8 μg/L; normal < 30 μg/L) but not in the other treatment groups (P < .001 for all comparisons vs voriconazole). We conclude that serum fluoride levels were elevated on average 5-fold above normal levels in hematologic patients receiving voriconazole. Clinically relevant skeletal disease was associated with renal insufficiency and above 10-fold elevated fluoride levels, and was reversible on termination of voriconazole treatment. 相似文献
128.
129.
130.
Léonie Egli Virgile Lecoultre Fanny Theytaz Vanessa Campos Leanne Hodson Philippe Schneiter Bettina Mittendorfer Bruce W. Patterson Barbara A. Fielding Philipp A. Gerber Vittorio Giusti Kaspar Berneis Luc Tappy 《Diabetes》2013,62(7):2259-2265
Excess fructose intake causes hypertriglyceridemia and hepatic insulin resistance in sedentary humans. Since exercise improves insulin sensitivity in insulin-resistant patients, we hypothesized that it would also prevent fructose-induced hypertriglyceridemia. This study was therefore designed to evaluate the effects of exercise on circulating lipids in healthy subjects fed a weight-maintenance, high-fructose diet. Eight healthy males were studied on three occasions after 4 days of 1) a diet low in fructose and no exercise (C), 2) a diet with 30% fructose and no exercise (HFr), or 3) a diet with 30% fructose and moderate aerobic exercise (HFrEx). On all three occasions, a 9-h oral [13C]-labeled fructose loading test was performed on the fifth day to measure [13C]palmitate in triglyceride-rich lipoprotein (TRL)-triglycerides (TG). Compared with C, HFr significantly increased fasting glucose, total TG, TRL-TG concentrations, and apolipoprotein (apo)B48 concentrations as well as postfructose glucose, total TG, TRL-TG, and [13C]palmitate in TRL-TG. HFrEx completely normalized fasting and postfructose TG, TRL-TG, and [13C]palmitate concentration in TRL-TG and apoB48 concentrations. In addition, it increased lipid oxidation and plasma nonesterified fatty acid concentrations compared with HFr. These data indicate that exercise prevents the dyslipidemia induced by high fructose intake independently of energy balance.It is currently suspected that overconsumption of fructose, in the form of either sugar or high-fructose corn syrup, may promote obesity and favor the development of metabolic diseases such as type 2 diabetes and dyslipidemia (1,2). This is supported by a large number of studies in rodents, which demonstrate that a high-sucrose diet causes obesity, diabetes, dyslipidemia, and hepatic steatosis (3) and that this effect is mainly due to the fructose component of sucrose (4,5). Consistent with this hypothesis, epidemiological studies have shown that high intakes of sugar, fructose, or sweetened beverages are associated with the development of obesity (6,7), diabetes (8), hypertriglyceridemia (9), an increase in small dense atherogenic LDL particles (10), high blood pressure (11), albuminuria (12), and nonalcoholic fatty liver diseases (13). Several short-term studies have further documented that hypercaloric, high-fructose diets can cause increases in a number of cardiometabolic risk factors in humans, such as fasting and postprandial hypertriglyceridemia (14–18), ectopic lipid deposition in liver cells (19,20), impaired postprandial glucose homeostasis (18), and hepatic insulin resistance (21,22). Some of these effects may be related, at least in part, to the fact that fructose can be converted into fatty acids, which has been demonstrated after both acute (23) and chronic (18) fructose feeding. Exercise is very efficient at reducing the metabolic dysfunctions associated with obesity (24,25), and although many of these effects appear to be related to enhanced energy expenditure and improved energy balance (26,27), there is growing evidence that such improvements are independent of the changes in energy balance or body composition (28,29). Exercise has also been shown to prevent the accumulation of triglyceride-rich lipoprotein (TRL)-triglycerides (TG) and improve the plasma atherogenic lipid profile in healthy subjects fed a high-carbohydrate diet (30). The purpose of this study was to investigate whether exercise would similarly prevent fructose-induced metabolic effects. 相似文献