全文获取类型
收费全文 | 3170篇 |
免费 | 171篇 |
国内免费 | 9篇 |
专业分类
耳鼻咽喉 | 16篇 |
儿科学 | 116篇 |
妇产科学 | 73篇 |
基础医学 | 356篇 |
口腔科学 | 73篇 |
临床医学 | 289篇 |
内科学 | 670篇 |
皮肤病学 | 57篇 |
神经病学 | 142篇 |
特种医学 | 101篇 |
外科学 | 468篇 |
综合类 | 45篇 |
一般理论 | 2篇 |
预防医学 | 145篇 |
眼科学 | 80篇 |
药学 | 386篇 |
中国医学 | 9篇 |
肿瘤学 | 322篇 |
出版年
2023年 | 25篇 |
2022年 | 67篇 |
2021年 | 148篇 |
2020年 | 56篇 |
2019年 | 78篇 |
2018年 | 105篇 |
2017年 | 78篇 |
2016年 | 70篇 |
2015年 | 73篇 |
2014年 | 120篇 |
2013年 | 156篇 |
2012年 | 269篇 |
2011年 | 254篇 |
2010年 | 133篇 |
2009年 | 153篇 |
2008年 | 183篇 |
2007年 | 178篇 |
2006年 | 138篇 |
2005年 | 139篇 |
2004年 | 137篇 |
2003年 | 139篇 |
2002年 | 85篇 |
2001年 | 53篇 |
2000年 | 55篇 |
1999年 | 48篇 |
1998年 | 26篇 |
1997年 | 16篇 |
1996年 | 17篇 |
1995年 | 13篇 |
1992年 | 20篇 |
1991年 | 22篇 |
1990年 | 23篇 |
1989年 | 21篇 |
1988年 | 20篇 |
1987年 | 26篇 |
1986年 | 20篇 |
1985年 | 19篇 |
1984年 | 13篇 |
1983年 | 18篇 |
1982年 | 7篇 |
1979年 | 18篇 |
1978年 | 6篇 |
1977年 | 8篇 |
1976年 | 7篇 |
1975年 | 7篇 |
1974年 | 11篇 |
1973年 | 11篇 |
1972年 | 6篇 |
1971年 | 11篇 |
1969年 | 6篇 |
排序方式: 共有3350条查询结果,搜索用时 15 毫秒
51.
Ibrutinib has revolutionized the treatment of chronic lymphocytic leukemia (CLL). This drug irreversibly inhibits Bruton tyrosine kinase (BTK) by covalently binding to the C481 residue in the BTK kinase domain. BTK is a pivotal protein for B cell receptor signaling and tissue homing of CLL cells. Preclinical investigations have established the importance of the B cell receptor pathway in the maintenance and survival of normal and malignant B cells, underscoring the importance of targeting this axis for CLL. Clinical trials demonstrated overall and progression-free survival benefit with ibrutinib in multiple CLL subgroups, including patients with relapsed or refractory disease, patients with 17p deletion, elderly patients, and treatment-naïve patients. Consequently, ibrutinib was approved by the US Food and Drug Administration for newly diagnosed and relapsed disease. Ibrutinib has transformed the treatment of CLL; however, several limitations have been identified, including low complete remission rates, development of resistance, and uncommon substantial toxicities. Further, ibrutinib must be used until disease progression, which imposes a financial burden on patients and society. These limitations were the impetus for the development of ibrutinib combinations. Four strategies have been tested in recent years: combinations of ibrutinib with immunotherapy, chemoimmunotherapy, cell therapy, and other targeted therapy. Here, we review the scientific rationale for and clinical outcome of each strategy. Among these strategies, ibrutinib with targeted agent venetoclax results in high complete response rates and, importantly, high rates of undetectable minimal residual disease. Although we concentrate here on ibrutinib, similar combinations are expected or ongoing with acalabrutinib, tirabrutinib, and zanubrutinib, second-generation BTK inhibitors. Future investigations will focus on the feasibility of discontinuing ibrutinib combinations after a defined time; the therapeutic benefit of adding a third agent to ibrutinib-containing combinations; and profiling of resistant clones that develop after combination treatment. A new standard of care for CLL is expected to emerge from these investigations.Subject terms: Combination drug therapy, Medical research 相似文献
52.
Payam Sajedi Lydia Chelala Joel Nunez-Gonalez Carolyn Cronin Steven Kittner Jiachen Zhuo Yang Zhang Dheeraj Gandhi Prashant Raghavan 《Journal of neuroradiology. Journal de neuroradiologie》2019,46(2):136-140
Background and purpose
Carotid webs are intraluminal filling defects at the carotid bulb which are considered rare, though possibly underappreciated entities with recent studies demonstrating a likely casual association with ischemic stroke. The purpose of the study is to describe our recent experience with clinical and imaging manifestations of carotid webs.Materials and methods
A retrospective review of CTA neck studies in all adult patients presenting to our institution during the 19-month study interval was performed to determine the presence of carotid webs. Subsequent chart review of these patients with webs was performed to assess their clinical history and to obtain demographic detail.Results
A total of 14 patients were identified with carotid webs in the study population. The mean age of patients with webs was 42.1?years (range: 28–54), consisting mostly of African Americans (86%) and females (64%). Ten (71%) of web patients had a history of ischemic stroke, each ipsilateral to the side of web, and at least four of these patients had recurrent ischemic stroke.Conclusion
We provide one of the largest sample sizes of webs gathered in a single study. Given its association with ischemic stroke, carotid webs should be assessed for in all patients presenting with ischemic stroke, especially younger African Americans. 相似文献53.
ObjectiveTo evaluate the effects of Montelukast and Curcumin against indomethacin induced gastric damage in rats in order to assess the role of leukotriene (LTs) if any, in non steroidal anti-inflammatory drug (NSAID) induced gastroinflammation.MethodsThe effects of Montelukast (10 mg/kg) and Curcumin (100 mg/kg) were observed on gastric lesion induced by Indomethacin. The blood samples were analyzed for neutrophil adhesion and lipid peroxide levels in gastric tissue measured spectrophotometrically. The skin vascular permeability study was performed by using compound 48/80 induced vascular permeability model.ResultsMontelukast and Curcumin significantly reduced Indomethacin induced gastric lesion score. Pretreatment with Montelukast and Curcumin significantly counteracted Indomethacin induced gastropathy by a combination of its effect on inhibition of neutrophil adherence, through decrease in related production of free radicals that disrupts integrity of stomach mucosa and decrease in vascular permeability as compared to Indomethacin group. The results of the present study further indicates the role of 5-LOX metabolites in NSAIDs induced gastro inflammation and suggests that Montelukast and Curcumin counteracted the Indomethacin induced gastropathy by a combination of its effect on inhibition of neutrophil adherence and through decrease in related production of free radicals that disrupts integrity of stomach mucosa.ConclusionsExperimental data clearly demonstrated the role of LTs was indomethacin induced gastric ulcers. However, inhibition of ulcerogenic events by Montelukast and Curcumin is suggestive of an important balance between COX and 5-LOX products. 相似文献
54.
Pawan Sinha Margaret M. Kjelgaard Tapan K. Gandhi Kleovoulos Tsourides Annie L. Cardinaux Dimitrios Pantazis Sidney P. Diamond Richard M. Held 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(42):15220-15225
A rich collection of empirical findings accumulated over the past three decades attests to the diversity of traits that constitute the autism phenotypes. It is unclear whether subsets of these traits share any underlying causality. This lack of a cohesive conceptualization of the disorder has complicated the search for broadly effective therapies, diagnostic markers, and neural/genetic correlates. In this paper, we describe how theoretical considerations and a review of empirical data lead to the hypothesis that some salient aspects of the autism phenotype may be manifestations of an underlying impairment in predictive abilities. With compromised prediction skills, an individual with autism inhabits a seemingly “magical” world wherein events occur unexpectedly and without cause. Immersion in such a capricious environment can prove overwhelming and compromise one’s ability to effectively interact with it. If validated, this hypothesis has the potential of providing unifying insights into multiple aspects of autism, with attendant benefits for improving diagnosis and therapy. 相似文献
55.
56.
A prospective study was carried out to assess the role of citric acid as a sole antimicrobial agent in the management of lepromatous ulcers. Thirty-four known cases of lepromatous ulcers not responding to conventional antibiotic therapies for long duration were investigated for culture and susceptibility studies. Staphylococcus aureus (25·00%) and Klebsiella spp. (23·43%) were found to be the most common isolates. Amikacin (68·75%) and ciprofloxacin (67·18%) were found to be the most effective antimicrobial agents. Topical application of citric acid ointment resulted in complete healing in 25 (73·52%) cases. In eight cases (26·48%), there was elimination of infective agent from ulcer site and formation of healthy granulation, but no complete healing of ulcer was seen. Results indicate that citric acid is the best alternative for the effective management of lepromatous ulcers when other therapies are exhausted. 相似文献
57.
Anand N. Shukla Bhavesh Thakkar Ashwal A. Jayaram Tarun H. Madan Gaurav D. Gandhi 《Journal of thrombosis and thrombolysis》2014,38(1):24-29
Pulmonary embolism (PE) is a relatively common life-threatening cardiovascular condition associated with significant morbidity and mortality. We present the efficacy and safety data of weight-adjusted tenecteplase in 30 consecutive patients of acute PE. 30 patients (22 male, 8 female) with acute PE were included in the study and divided into three groups: (1) Acute PE complicated by shock stage and/or persistent hypotension (12 patients). (2) RV dilatation and/or dysfunction without hypotension (14 patients). (3) Severe hypoxemia without hypotension and RV dysfunction (4 patients). Predominant symptoms were dyspnoea, cough, chest pain, syncope and haemoptysis, noted in 100 % (30), 40 % (12), 54 % (16), 32 % (9) and 10 % (3) of patients respectively. RV dilatation and dyskinesia were present in 86 %, septal paradoxical movement in 73 % and inferior venacava collapse absent in 53 % of patients respectively. 12 patients presented with acute PE and cardiogenic shock, 14 patients showed RV dilatation and dysfunction with systolic BP >90 mmHg and four patients were having RV dilation without dysfunction but severe hypoxemia. There was significant reduction in right ventricular systolic pressure and improvement in right ventricular dysfunction. Our study shows that tenecteplase is very effective and safe in the treatment of PE with minimal risk of bleeding in high risk group and intermediate risk and even in selective low risk category group of patients. However, in view of small number of patients in study group, a large multicentre randomized study would be required to draw a firm conclusion regarding the thrombolysis in low risk category patient. 相似文献
58.
59.
60.
Margaret F. Keil† Deborah P. Merke†‡§ Roma Gandhi Edythe A. Wiggs¶ Kathy Obunse§ Constantine A. Stratakis†‡ 《Clinical endocrinology》2009,71(3):326-333
Objective Cushing syndrome (CS) in children is associated with symptoms that may impair health related quality of life (HRQL). There are no prospective reports of HRQL in children with CS.
Methods Prospective study of 40 children (mean age 13 ± 3·2 years) with CS evaluated prior to and 1-year post-treatment. The Child Health Questionnaire (CHQ) was used to assess HRQL; Wechsler Intelligence Scale for Children (WASI) was used to assess cognitive function, and patient-reported symptoms were assessed with a CS symptom checklist.
Results Active CS was associated with low physical and psychosocial summary scores compared to US population data ( P < 0·001). Despite improvement from pre- to 1-year postcure, residual impairment remained in physical summary and function, and role-physical, global health and emotional impact (parent) scores. Incomplete recovery of adrenal function at 1-year post-treatment was associated with impaired scores. WASI IQ scores declined and a correlation was noted between age at first evaluation and IQ score changes. Most self-reported CS symptoms showed improvement, but forgetfulness, unclear thinking and decreased attention span did not improve after cure of CS.
Conclusion CS in children and adolescents is associated with impaired HRQL, with residual impairment 1 year after cure. Our results also suggest that younger children are more likely to experience negative changes in cognitive function. HRQL is an important outcome measure in children and adolescents with CS and identification of factors that contribute to HRQL may help to diminish the physical and psychological burden of disease in this population of patients. 相似文献
Methods Prospective study of 40 children (mean age 13 ± 3·2 years) with CS evaluated prior to and 1-year post-treatment. The Child Health Questionnaire (CHQ) was used to assess HRQL; Wechsler Intelligence Scale for Children (WASI) was used to assess cognitive function, and patient-reported symptoms were assessed with a CS symptom checklist.
Results Active CS was associated with low physical and psychosocial summary scores compared to US population data ( P < 0·001). Despite improvement from pre- to 1-year postcure, residual impairment remained in physical summary and function, and role-physical, global health and emotional impact (parent) scores. Incomplete recovery of adrenal function at 1-year post-treatment was associated with impaired scores. WASI IQ scores declined and a correlation was noted between age at first evaluation and IQ score changes. Most self-reported CS symptoms showed improvement, but forgetfulness, unclear thinking and decreased attention span did not improve after cure of CS.
Conclusion CS in children and adolescents is associated with impaired HRQL, with residual impairment 1 year after cure. Our results also suggest that younger children are more likely to experience negative changes in cognitive function. HRQL is an important outcome measure in children and adolescents with CS and identification of factors that contribute to HRQL may help to diminish the physical and psychological burden of disease in this population of patients. 相似文献