全文获取类型
收费全文 | 11052篇 |
免费 | 713篇 |
国内免费 | 51篇 |
专业分类
耳鼻咽喉 | 85篇 |
儿科学 | 181篇 |
妇产科学 | 131篇 |
基础医学 | 1513篇 |
口腔科学 | 580篇 |
临床医学 | 1077篇 |
内科学 | 2352篇 |
皮肤病学 | 130篇 |
神经病学 | 1157篇 |
特种医学 | 300篇 |
外国民族医学 | 1篇 |
外科学 | 1973篇 |
综合类 | 43篇 |
一般理论 | 3篇 |
预防医学 | 662篇 |
眼科学 | 191篇 |
药学 | 738篇 |
中国医学 | 51篇 |
肿瘤学 | 648篇 |
出版年
2023年 | 106篇 |
2022年 | 196篇 |
2021年 | 440篇 |
2020年 | 238篇 |
2019年 | 353篇 |
2018年 | 446篇 |
2017年 | 301篇 |
2016年 | 316篇 |
2015年 | 386篇 |
2014年 | 523篇 |
2013年 | 625篇 |
2012年 | 973篇 |
2011年 | 954篇 |
2010年 | 520篇 |
2009年 | 484篇 |
2008年 | 686篇 |
2007年 | 700篇 |
2006年 | 623篇 |
2005年 | 581篇 |
2004年 | 462篇 |
2003年 | 383篇 |
2002年 | 326篇 |
2001年 | 91篇 |
2000年 | 75篇 |
1999年 | 76篇 |
1998年 | 53篇 |
1997年 | 46篇 |
1996年 | 34篇 |
1995年 | 20篇 |
1994年 | 18篇 |
1993年 | 22篇 |
1992年 | 46篇 |
1991年 | 57篇 |
1990年 | 40篇 |
1989年 | 34篇 |
1988年 | 59篇 |
1987年 | 55篇 |
1986年 | 59篇 |
1985年 | 30篇 |
1984年 | 15篇 |
1983年 | 26篇 |
1982年 | 19篇 |
1980年 | 17篇 |
1979年 | 36篇 |
1978年 | 16篇 |
1977年 | 15篇 |
1975年 | 17篇 |
1974年 | 24篇 |
1973年 | 16篇 |
1972年 | 15篇 |
排序方式: 共有10000条查询结果,搜索用时 187 毫秒
101.
Abstract: The need to replace natural amino acids in peptides with nonproteinogenic counterparts to obtain new medicinal agents has stimulated a great deal of innovation on synthetic methods. Here, we report the incorporation of non‐natural silylated amino acids in substance P (SP), the binding affinity for the two hNK‐1 binding sites and, the potency to stimulate phospholipase C (PLC) and adenylate cyclase of the resulting peptide. We also assess the improvement of their stability towards enzyme degradation. Altogether, we found that replacing glycine with silaproline (Sip) in position 9 of SP leads to a potent analogue exhibiting an increased resistance to angiotensin‐converting enzyme hydrolysis. 相似文献
102.
Eric Raymond Carmen Kahatt Marie Hélène Rigolet William Sutherland Fran?ois Lokiec Jér?me Alexandre Bertrand Tombal Michael Elman Michael S Lee John R MacDonald Michael Cullen Jean-Louis Misset Esteban Cvitkovic 《Clinical cancer research》2004,10(22):7566-7574
PURPOSE: Irofulven (6-hydroxymethylacylfulvene) is a novel agent, derived from illudin S, with potent apoptotic effects in preclinical models. In the Phase I trial evaluating intermittent weekly schedules, visual symptoms were dose limiting. The aim of this analysis was to better characterize the visual adverse events of irofulven and provide treatment guidelines. EXPERIMENTAL DESIGN: Clinical data from 277 patients entered in single-agent Phase I to II clinical trials who received irofulven on days 1 and 15 every 4 weeks; days 1, 8, and 15 every 4 weeks; or days 1 and 8 every 3 weeks were included in this multiparameter analysis. RESULTS: Overall, 74 patients (27%) experienced visual symptoms. The most frequently reported symptoms were flashing lights (12% of patients), blurred vision (9%), and photosensitivity (8%). Grade 3 toxicity was observed in 12 patients (4%). The incidence and severity of visual events were dose dependent, with no grade 3 visual events occurring at doses < or =0.50 mg/kg and grade 1 to 2 events in only 12% and 8% of patients, at doses of < or =0.50 mg/kg and < or =20 mg/m2, respectively. Grade 1 to 2 toxicity was reversible in most patients. Abnormal electroretinogram and abnormal visual fields were noted after irofulven treatment in 24 of 39 patients (62%) and 15 of 26 patients (58%), respectively. All but 1 patient who had electroretinogram assessment received doses >0.50 mg/kg. Clinical examination and visual field assessment were found to be better correlated with symptoms and appear to be more appropriate for surveillance of irofulven retinal symptoms than electroretinograms. CONCLUSIONS: On the basis of retained antitumor activity and reversibility of grade 1 and 2 visual symptoms at lower doses, it appears that an irofulven dose of < or =0.50 mg/kg or < or =20 mg/m2, not to exceed 50 mg in a single dose, given as a 30-minute infusion on days 1 and 8 every 3 weeks or days 1 and 15 every 4 weeks minimizes the frequency and severity of visual symptoms. 相似文献
103.
Katherine DeLellis Sabina Rinaldi Rudolph J Kaaks Laurence N Kolonel Brian Henderson Loic Le Marchand 《Cancer epidemiology, biomarkers & prevention》2004,13(9):1444-1451
High circulating concentration of insulin-like growth factor-I (IGF-I) and low circulating concentration of IGF binding protein-3 (IGFBP-3) have been associated with increased risk for breast, prostate, and colorectal cancers. Building on previous work in the Multiethnic Cohort (MEC) showing significant differences in IGF-I levels across racial/ethnic groups, we investigated which lifestyle and dietary factors are associated with levels of IGF-I and IGFBP-3 in a random sample of 1,000 MEC participants, which included Native Hawaiian, African American, Japanese, Latino, and White men and women. Crude analyses confirmed the existence of differences in protein levels with race/ethnicity, sex, age, and body size. Reproductive, physical activity, smoking, and diet variables had less consistent effects. In multivariate analyses, IGF-I levels were lower and IGFBP-3 were higher in females versus males. IGF-I and IGFBP-3 declined with increasing age in both genders. Women in the highest quartile of body mass index showed depressed IGF-I and IGFBP-3 levels; in men, height was significantly positively associated with both proteins. In women, alcohol was directly associated with IGFBP-3. Both proteins were lowest among female Latinos. IGF-I was highest among female African Americans. In men, IGFBP-3 was lowest among African Americans. Overall, although these factors were statistically significant determinants of IGF-related protein levels, they did not explain much of the variation in these levels. A positive correlation was found between IGF-I levels (ng/mL) and colon cancer incidence rates (per 100,000) within the MEC by race/ethnicity for both sexes but not for either breast or prostate cancer. 相似文献
104.
J Alexandre M Gross-Goupil B Falissard M-L Nguyen J-M Gornet J-L Misset F Goldwasser 《Annals of oncology》2003,14(1):36-41
BACKGROUND: The toxicity outcome of cancer patients receiving chemotherapy is difficult to predict. In this study the influence of malnutrition and inflammation on acute haematological toxicity was investigated. PATIENTS AND METHODS: Between January 1999 and January 2000, 48 consecutive cancer patients experienced severe haematological toxicity (SHT), either neutropenic fever or severe thrombocytopenia, following various chemotherapy regimens. Their baseline characteristics were compared with those of 59 control patients. Previous chemotherapy regimens, type of chemotherapy, performance status (PS), calculated creatinine clearance, bilirubin, C-reactive protein (1), alpha-1 acid glycoprotein (2), albumin (3), pre-albumin (4) and the nutritional and inflammatory status (NIS) ratio [NIS = (1 x 2)/(3 x 4)] were studied. Statistical analysis was carried out using either a t-test or a chi-square test. A receiver operating characteristic (ROC) curve determined the cut-off value for NIS. RESULTS: Patients experiencing SHT had a higher PS (P <0.001), inflammatory serum protein levels (P <0.001) and NIS ratio (P <0.0001), but lower haemoglobin (P <0.05) and serum-albumin levels (P <0.0001). Using a cut-off of 0 or 1 for PS and 1 for NIS, sensitivity was 98%, 43% and 89%; specificity was 38%, 90% and 66%, respectively. In 37 patients treated with topotecan as single agent, the determinants for SHT were PS (P <0.0001) and NIS (P <0.0001). CONCLUSIONS: Altered nutritional and inflammatory status correlates with increased risk of severe haematological toxicity following anticancer chemotherapy. 相似文献
105.
The need to embrace molecular profiling of tumor cells in prostate and bladder cancer. 总被引:2,自引:0,他引:2
Brian J Duggan John J McKnight Kate E Williamson Maurice Loughrey Declan O'Rourke Peter W Hamilton Samuel R Johnston Claude C Schulman Alexandre R Zlotta 《Clinical cancer research》2003,9(4):1240-1247
PURPOSE: Current treatment strategies for urological cancer are still based on empirical formulae as opposed to treatment tailored for each cancer patient. To individualize treatment, the multiple molecular abnormalities within tumor cell populations needs to be mapped out. The aim of this article is to explain molecular profiling (MP) and its associated techniques so that the process is not purely seen as a research tool but as a future adjunctive measure in patient diagnosis and treatment. EXPERIMENTAL DESIGN: A Medline search of publications relating to MP of prostate and bladder cancer was carried out. A review article was written combining the relevant published literature along with the clinical and scientific experience of both centers. RESULTS: The advent of MP now provides a strategy by which these molecular abnormalities can be assessed. As well as being of diagnostic and prognostic use, these molecular profiles will identify putative molecular abnormalities within tumor cells that may be appropriate for therapeutic modulation. CONCLUSIONS: In prostate and bladder cancer, mapping out the molecular abnormalities could be translated into a valuable tool to help solve difficult issues regarding patient management decisions. 相似文献
106.
107.
Jean-Blaise Wasserfallen Alexandre Berger Philippe Eckert Jean-Christophe Stauffer Jürg Schlaepfer Dominique Gillis Jacques Cornuz Marie-Denise Schaller Lukas Kappenberger Bertrand Yersin 《International journal for quality in health care》2004,16(5):383-389
OBJECTIVE: To assess the impact of introducing clinical practice guidelines on acute coronary syndrome without persistent ST segment elevation (ACS) on patient initial assessment. DESIGN: Prospective before-after evaluation over a 3-month period. SETTING: The emergency ward of a tertiary teaching hospital. PATIENTS: All consecutive patients with ACS evaluated in the emergency ward over the two 3-month periods. INTERVENTION: Implementation of the practice guidelines, and the addition of a cardiology consultant to the emergency team. MAIN OUTCOME MEASURES: Diagnosis, electrocardiogram interpretation, and risk stratification after the initial evaluation. RESULTS: The clinical characteristics of the 328 and 364 patients evaluated in the emergency ward for suspicion of ACS before and after guideline implementation were similar. Significantly more patients were classified as suffering from atypical chest pain (39.6% versus 47.0%; P = 0.006) after guideline implementation. Guidelines availability was associated with significantly more formal diagnoses (79.9% versus 92.9%; P < 0.0001) and risk stratification (53.7% versus 65.4%, P < 0.0001) at the end of initial assessment. CONCLUSION: Guidelines implementation, along with availability of a cardiology consultant in the emergency room had a positive impact on initial assessment of patients evaluated for suspicion of ACS. It led to increased confidence in diagnosis and stratification by risk, which are the first steps in initiating effective treatment for this common condition. 相似文献
108.
Sandhi Maria Barreto Luana Giatti Alexandre Kalache 《Pan American journal of public health》2004,16(2):110-117
OBJECTIVE: To investigate gender differences among older Brazilians in their health status and their use of health services. METHODS: Participants were individuals aged 60 years and older included in a national household survey conducted in Brazil in 1998. Data were analyzed by multiple logistic regression, taking into account the design effect due to multistage sampling. RESULTS: There were differences in the health and living conditions of older men and older women that were not explained by age or place of residence. Older women had worse indicators of schooling and personal income but better indicators of housing standards and per capita household income. The older women also reported more chronic diseases, had poorer indicators of independence and physical mobility, sought health services more often, and reported more medical visits in the previous year. Despite their apparent worse health conditions, elderly women in urban areas had lower hospitalization rates in the previous year (odds ratio = 0.89; 95% confidence interval, 0.82-0.96) than did elderly men in urban areas. CONCLUSIONS: Our results indicate that among older Brazilians there are gender inequalities in health that cannot be explained by age and place of residence. The findings raise questions on how health, socioeconomic, and cultural factors influence gender patterns of seeking and using health care in later life in the country. As pressures on health care and health funding increase in Brazil as a result of the aging of the population, there is a need to take a gender perspective into account. 相似文献
109.
Alexandre T Rotta Mário Eduardo G Viana Budi Wiryawan Guilherme A Sargentelli Mark S Dowhy Walter A Zin Bradley P Fuhrman 《Pediatric critical care medicine》2006,7(6):562-570
OBJECTIVE: To evaluate the independent and combined effects of high-frequency oscillatory ventilation (HFOV) and partial liquid ventilation (PLV) on gas exchange, pulmonary histopathology, inflammation, and oxidative tissue damage in an animal model of acute lung injury. DESIGN: Prospective, randomized animal study. SETTING: Research laboratory of a health sciences university. SUBJECTS: Fifty New Zealand White rabbits. INTERVENTIONS: Juvenile rabbits injured by lipopolysaccharide infusion and saline lung lavage were assigned to conventional ventilation (CMV), PLV, HFOV, or high-frequency partial liquid ventilation (HF-PLV) with a full or half dose (HF-PLV1/2) of perfluorochemical (PFC). Uninjured ventilated animals served as controls. Arterial blood gases were obtained every 30 mins during the 4-hr study. Histopathologic evaluation was performed using a lung injury scoring system. Oxidative lung injury was assessed by measuring malondialdehyde and 4-hydroxynonenal in lung homogenates. MEASUREMENTS AND MAIN RESULTS: HFOV, PLV, or a combination of both methods (HF-PLV) resulted in significantly improved oxygenation, more favorable lung histopathology, reduced neutrophil infiltration, and attenuated oxidative damage compared with CMV. HF-PLV with a full PFC dose did not provide any additional benefit compared with HFOV alone. HF-PLV1/2 was associated with decreased pulmonary leukostasis compared with HF-PLV. CONCLUSIONS: The combination of HFOV and PLV (HF-PLV) does not provide any additional benefit compared with HFOV or PLV alone in a combined model of lung injury when lung recruitment and volume optimization can be achieved. The use of a lower PFC dose (HF-PLV1/2) is associated with decreased pulmonary leukostasis compared with HF-PLV and deserves further study. 相似文献
110.
Cháriston André Dal Belo Gildo Bernardo Leite Marcos Hikari Toyama Sergio Marangoni Alexandre Pinto Corrado Marcos Dias Fontana Andy Southan Edward G Rowan Stephen Hyslop Léa Rodrigues-Simioni 《Toxicon》2005,46(7):736-750
We have isolated a new phospholipase A2 (MiDCA1) from the venom of the coral snake Micrurus dumerilii carinicauda. This toxin, which had a molecular mass of 15,552Da, shared high sequence homology with the PLA2 toxins MICNI A and B from Micrurus nigrocinctus venom (77.7% and 73.1%, respectively). In chick biventer cervicis preparations, MiDCA1 produced concentration- and time-dependent neuromuscular blockade that reached 100% after 120 min (2.4 microM, n = 6); contractures to exogenously applied carbachol (8 microM) and KCl (13 mM) were still seen after complete blockade. In mouse phrenic-nerve diaphragm preparations, MiDCA1 (2.4 microM; n = 6) caused triphasic changes followed by partial neuromuscular blockade. Intracellular recordings of end-plate potentials (EPPs) and miniature end-plate potentials (MEPPs) from mouse diaphragm preparations showed that MiDCA1 increased the quantal content by 386+/-12% after 10 min (n = 14; p<0.05) and caused a triphasic change in the frequency of MEPPs. MiDCA1 also decreased the resting membrane potential, an effect that was prevented by tetrodotoxin and/or low extracellular calcium, but not by d-tubocurarine. The toxin increased the amplitude of mouse sciatic-nerve compound action potentials by 30+/-9% (0.6 microM; p<0.05). Potassium currents elicited in freshly dissociated dorsal root ganglia neurones were blocked by 31+/-1% (n = 4; p<0.05) in the presence of 2.4 microM MiDCA1. These results show that MiDCA1 is a new presynaptic phospholipase A2 that produces neuromuscular blockade in vertebrate nerve-muscle preparations. The triphasic effects seen in mammalian preparations and the facilitatory response were probably caused mainly by the activation of sodium channels, complemented by the blockade of nerve terminal potassium channels. The inability of d-turocurarine to prevent the depolarization by MiDCA1 indicated that cholinergic nicotinic receptors were not involved in this phenomenon. 相似文献