全文获取类型
收费全文 | 4135篇 |
免费 | 174篇 |
国内免费 | 39篇 |
专业分类
耳鼻咽喉 | 20篇 |
儿科学 | 87篇 |
妇产科学 | 89篇 |
基础医学 | 495篇 |
口腔科学 | 103篇 |
临床医学 | 284篇 |
内科学 | 1090篇 |
皮肤病学 | 84篇 |
神经病学 | 421篇 |
特种医学 | 144篇 |
外科学 | 682篇 |
综合类 | 22篇 |
预防医学 | 224篇 |
眼科学 | 26篇 |
药学 | 237篇 |
中国医学 | 25篇 |
肿瘤学 | 315篇 |
出版年
2024年 | 4篇 |
2023年 | 30篇 |
2022年 | 72篇 |
2021年 | 126篇 |
2020年 | 69篇 |
2019年 | 91篇 |
2018年 | 137篇 |
2017年 | 78篇 |
2016年 | 97篇 |
2015年 | 125篇 |
2014年 | 169篇 |
2013年 | 248篇 |
2012年 | 302篇 |
2011年 | 326篇 |
2010年 | 205篇 |
2009年 | 163篇 |
2008年 | 307篇 |
2007年 | 274篇 |
2006年 | 251篇 |
2005年 | 272篇 |
2004年 | 229篇 |
2003年 | 201篇 |
2002年 | 193篇 |
2001年 | 32篇 |
2000年 | 27篇 |
1999年 | 17篇 |
1998年 | 37篇 |
1997年 | 27篇 |
1996年 | 30篇 |
1995年 | 21篇 |
1994年 | 19篇 |
1993年 | 18篇 |
1992年 | 14篇 |
1991年 | 14篇 |
1990年 | 9篇 |
1989年 | 11篇 |
1988年 | 16篇 |
1987年 | 13篇 |
1986年 | 7篇 |
1985年 | 7篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1982年 | 8篇 |
1981年 | 4篇 |
1980年 | 8篇 |
1977年 | 3篇 |
1975年 | 3篇 |
1971年 | 2篇 |
1969年 | 3篇 |
1931年 | 2篇 |
排序方式: 共有4348条查询结果,搜索用时 46 毫秒
61.
G-protein-coupled receptors (GPCRs), which represent the largest gene family in the human genome, play a crucial role in multiple physiological functions as well as in tumor growth and metastasis. For instance, various molecules like hormones, lipids, peptides and neurotransmitters exert their biological effects by binding to these seven-transmembrane receptors coupled to heterotrimeric G-proteins, which are highly specialized transducers able to modulate diverse signaling pathways. Furthermore, numerous responses mediated by GPCRs are not dependent on a single biochemical route, but result from the integration of an intricate network of transduction cascades involved in many physiological activities and tumor development. This review highlights the emerging information on the various responses mediated by a selected choice of GPCRs and the molecular mechanisms by which these receptors exert a primary action in cancer progression. These findings provide a broad overview on the biological activity elicited by GPCRs in tumor cells and contribute to the identification of novel pharmacological approaches for cancer patients. 相似文献
62.
63.
64.
Mario Musella Marco Milone Marcello Bellini Miguel Emilio Sosa Fernandez Loredana Maria Sosa Fernandez Maddalena Leongito Francesco Milone 《Obesity surgery》2011,21(4):426-430
The prevalence of people who are overweight or obese has increased dramatically in high-income countries over the past 20 years.
There is a strong association between obesity and infertility, and weight loss can result in increased fecundity in obese
women. The aim of this study is to demonstrate the potential role of intragastric balloon in the treatment of obese-related
infertility. This is a retrospective study. A chart review of 27 obese women seen between September 2003 and July 2008 was
performed. They all presented with the diagnosis of infertility and had undergone endoscopic intragastric balloon positioning.
Among these women who tried unsuccessfully to become pregnant before weight loss, 15 became pregnant afterward. The pregnancies
proceeded without complications and ended with live births. An improvement in the fertility status after weight loss has been
described, although data on fertility after weight loss following bariatric surgery are still limited. The results obtained
in our experience are not different from data reported in literature for bariatric surgery. Therefore, balloon treatment might
be effective in young infertile obese women who wish to become pregnant. 相似文献
65.
Fulvio Bruni Anna Laura Pasqui Marcello Pastorelli Giovanni Bova Michela Cercignani Alberto Palazzuoli Tatsuya Sawamura W R Gioffre Alberto Auteri Luca Puccetti 《Clinical and applied thrombosis/hemostasis》2005,11(4):417-428
Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular mortality by decreasing cholesterol as well as by non-lipid-related actions. Oxidized low-density lipoproteins (ox-LDL) are pro-atherogenic molecules and potent platelet agonists. CD36 and lectin-like ox-LDL receptor-1 (LOX-1) are specific ox-LDL receptors also expressed in platelets. This study was planned to address whether treatment with atorvastatin 10 mg/day, pravastatin 40 mg/day or simvastatin 20 mg/day could affect platelet CD36 and LOX-1 expression. Twenty-four patients for each treatment were evaluated after 3, 6, and 9 days and at 6 weeks for complete lipid profile (chromogenic), ox-LDL (ELISA), platelet P-selectin (P-sel), CD36, LOX-1 (FACS), and intracellular citrullin recovery (iCit) (HPLC). Data show hyperactivated platelets (P-sel absolute values, percent variation in activated cells, all p < 0.001), and CD36 and LOX-1 overexpression (all p < 0.001) in patients at baseline. P-sel, CD36, and LOX-1 were significantly decreased by atorvastatin and simvastatin (all p < 0.01) and related with iCit increase (r = 0.58, p < 0.001) and platelet-associated ox-LDL (r = 0.51, p < 0.01) at 9 days. Pravastatin reduced LOX-1 and P-sel (p < 0.05) at 6 weeks in relation with decreased LDL and ox-LDL (r = 0.39, p < 0.01 and r = 0.37, p < 0.01, respectively). These data suggest that atorvastatin and simvastatin reduce platelet activity by exposure of CD36 and LOX-1 before significant LDL reduction, whereas pravastatin action is detected later and in relation with LDL and ox-LDL lowering. Rapid and consistent reduction of CD36 and LOX-1 could be considered a direct anti-atherothrombotic mechanism related to the role of ox-LDL in platelet activation, platelet-endothelium interactions, and NO synthase activity. 相似文献
66.
Wenjie Wang Brendan Murphy Serdar Yilmaz Marcello Tonelli Jennifer MacRae Braden J. Manns 《Clinical journal of the American Society of Nephrology》2008,3(1):78-84
Background and objectives: Concern about primary fistula failure may contribute to the underuse of arteriovenous fistula. The objective of this study was to investigate the baseline clinical parameters associated with primary fistula success.Design, setting, participants, & measurements: Consecutive incident patients who commenced dialysis during a 28-mo period in a regional renal program were studied. Data on patient-related variables and on surgical approach (e.g., whether the surgeons routinely assess vessel size during the operation) were collected. Primary fistula success was defined as an arteriovenous fistula that was able to afford successful dialysis for 3 h with blood pump speed of ≥300 ml/min for three consecutive sessions.Results: A total of 205 (69%) patients had an AVF attempted as their first vascular access. The overall primary success rate was 64% and was similar for radiocephalic and brachiocephalic fistula. Logistic regression was done separately for patients with the two types of fistula because of the presence of statistical interaction. For radiocephalic fistula, male gender was the only parameter associated with primary fistula success (odds ratio 3.57; P = 0.01). The presence of comorbidity was not significantly associated with primary fistula failure.Conclusions: Despite significant patient comorbidity, there was a high primary fistula success rate among this incident hemodialysis cohort. Given that vessel size may be the ultimate determinant of fistula success, if surgeons assess vessel size perioperatively, then the presence of significant comorbidity might not preclude arteriovenous fistula from being attempted as the initial access.Given the well-documented advantages of arteriovenous fistula (AVF) over arteriovenous graft and central venous catheter (CVC), the current Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines suggest that AVF should be attempted as the initial vascular access in at least 50% of incident patients and that at least 40% of prevalent hemodialysis (HD) patients should undergo dialysis with an AVF (1–5). Despite these recommendations, it is clear that AVF are underused in many centers in North America, especially when compared with European centers (6,7). Recent data suggest that only 32% of prevalent US HD patients undergo dialysis with an AVF (8). In Canada, AVF are used by 53% of prevalent and only 26% of incident HD patients (7).One of the fears that may reduce the use of AVF is the high primary fistula failure rate (i.e., failure of AVF to mature) (9). Identifying risk factors that contribute to primary fistula failure may help clinicians and patients make an informed decision as to for whom to attempt an AVF. Only a few studies have prospectively examined the risk factors associated with primary fistula failure, which has been reported in 20 to 50% of patients (9–12).Most studies that have evaluated factors that are associated with primary fistula failure have typically used a retrospective design. For instance, Miller et al. (10) reported higher primary fistula failure rate in older and female patients with diabetes, although small numbers and a highly selected patient population limit the generalizability of these results. Feldman et al. (13) published data from a larger cohort (348 patients), reporting a primary success rate of 54%. Preexisting cerebrovascular disease, older age, and commencement of dialysis before access creation were noted to be associated with higher primary fistula failure in their study. Ravani et al. (11) noted that cardiovascular disease and late referral to nephrologists were associated with lower primary AVF success in patients from northern Italy.More recently, Lok et al. (14) studied a cohort of 422 HD patients who were undergoing their first AVF placement to identify preoperative clinical characteristics that are predictive of fistula failure to mature and to use this information to develop a prediction rule to estimate the risk for fistula failure to mature. This prediction rule was validated in an external data set from five North American centers. Age, peripheral vascular disease, coronary artery disease, and white race all were associated with fistula failure to mature in their study; however, in this and the previously mentioned studies, it is not clear whether there was any consistent surgical assessment performed perioperatively to guide fistula placement; as such, the results may not be applicable to programs that use pre- or intraoperative surgical assessment to guide fistula placement.Given these uncertainties, we sought to determine the association of various baseline clinical parameters with primary fistula success in a cohort that consisted of all incident dialysis patients between July 1, 1999, and November 1, 2001, in Calgary, Alberta, Canada, the majority of whom had an indirect assessment of vessel diameter intraoperatively to guide the location of fistula placement. 相似文献
67.
68.
High Prevalence of Helicobacter pylori in Liver Cirrhosis (Relationship with Clinical and Endoscopic Features and the Risk of Peptic Ulcer) 总被引:14,自引:0,他引:14
Mario Miglioli Roberto Corinaldesi Luigi Bolondi Sebastiano Siringo Dino Vaira Marcello Menegatti Fabio Piscaglia Soccorsa Sofia Mariana Gaetani 《Digestive diseases and sciences》1997,42(10):2024-2030
In 153 consecutive patients with cirrhosis weassessed: (1) the prevalence of IgG to Helicobacterpylori and compared it with that found in 1010 blooddonors resident in the same area; and (2) therelationships of IgG to Helicobacter pylori with clinical andendoscopic features and with the risk of peptic ulcer.The IgG to Helicobacter pylori prevalence of cirrhoticswas significantly higher than in blood donors (76.5% vs 41.8%; P < 0.0005) and was notassociated with sex, cirrhosis etiology, Child class,gammaglobulins and hypertensive gastropathy. In bothgroups, the prevalence of IgG to Helicobacter pylori was significantly higher in subjects over 40. Amongpatients with cirrhosis a significantly higherprevalence of Helicobacter pylori was found in patientswith previous hospital admission (P = 0.02) and/or upper gastrointestinal endoscopy (P = 0.01) andpatients with peptic ulcer (P = 0.0004). Multivariateanalysis identified increasing age and male sex as riskfactors for a positive Helicobacter pylori serology and no independent risk factors for pepticulcer. The high prevalence of Helicobacterpylori-positive serology found in the present series isrelated to age and sex and might also be explained byprevious hospital admissions and/or uppergastrointestinal endoscopy. Our results do not confirmthe role of Helicobacter pylori as risk factor forpeptic ulcer in patients with liver cirrhosis. 相似文献
69.
The insulin-like growth factor I receptor (IGF-IR) is expressed in many cell types and is critical for normal growth and development.
In the healthy mammary gland, the role of IGF-IR is not fully elucidated. However, IGF-IR, which is primarily expressed in
the mammary epithelial cells, is known to play an obligatory role in cellular transformation, facilitating the progression
to breast cancer. We have utilized the tetracycline regulatory (tet-on) system to generate an in vitro model system to allow
us to further investigate IGF-I/IGF-IR function in mammary epithelial cells. A plasmid construct containing a mutant IGF-I
receptor (IGF-IR-DN) fused to the tetracycline operator (tetOPhCMV-IGF-IR-DN) was stably transfected into MCF-7 human breast cancer cells. The conditional regulation of the IGF-IR-DN gene
expression was studied in four independent clonal lines. The translated IGF-IR-DN protein was detected only in the stably
transfected doxycycline-induced cells, and its expression was up-regulated (three- to sixfold) following induction. IGF-I
stimulated cell proliferation diminished (twofold) in doxycycline-induced cells compared to uninduced cells, demonstrating
that the transgene construct was functional and ruling out any pleiotropic effect that may be attributed to doxycycline. Interestingly,
autophosphorylation of the IGF-IR and phosphorylation of the downstream substrate, insulin receptor substrate-1 (IRS-1), was
not inhibited in doxycycline/IGF-I treated cells, suggesting the possibility that activation of downstream substrates other
than the IRS-1 may be critical for optimal cell proliferation. This novel in vitro model should allow us to more directly
examine the role of IGF-I/IGF-IR signaling and function in mammary epithelial cells. 相似文献