全文获取类型
收费全文 | 22911篇 |
免费 | 1506篇 |
国内免费 | 98篇 |
专业分类
耳鼻咽喉 | 232篇 |
儿科学 | 601篇 |
妇产科学 | 457篇 |
基础医学 | 3615篇 |
口腔科学 | 549篇 |
临床医学 | 2186篇 |
内科学 | 5121篇 |
皮肤病学 | 568篇 |
神经病学 | 2617篇 |
特种医学 | 673篇 |
外科学 | 2066篇 |
综合类 | 114篇 |
一般理论 | 13篇 |
预防医学 | 1957篇 |
眼科学 | 445篇 |
药学 | 1422篇 |
中国医学 | 80篇 |
肿瘤学 | 1799篇 |
出版年
2024年 | 36篇 |
2023年 | 217篇 |
2022年 | 418篇 |
2021年 | 737篇 |
2020年 | 487篇 |
2019年 | 693篇 |
2018年 | 758篇 |
2017年 | 574篇 |
2016年 | 678篇 |
2015年 | 787篇 |
2014年 | 937篇 |
2013年 | 1173篇 |
2012年 | 1886篇 |
2011年 | 1997篇 |
2010年 | 1065篇 |
2009年 | 967篇 |
2008年 | 1588篇 |
2007年 | 1570篇 |
2006年 | 1469篇 |
2005年 | 1373篇 |
2004年 | 1270篇 |
2003年 | 1153篇 |
2002年 | 993篇 |
2001年 | 162篇 |
2000年 | 132篇 |
1999年 | 155篇 |
1998年 | 196篇 |
1997年 | 169篇 |
1996年 | 122篇 |
1995年 | 96篇 |
1994年 | 78篇 |
1993年 | 68篇 |
1992年 | 61篇 |
1991年 | 48篇 |
1990年 | 51篇 |
1989年 | 36篇 |
1988年 | 34篇 |
1987年 | 32篇 |
1986年 | 25篇 |
1985年 | 23篇 |
1984年 | 21篇 |
1983年 | 22篇 |
1982年 | 11篇 |
1981年 | 14篇 |
1980年 | 17篇 |
1979年 | 11篇 |
1978年 | 11篇 |
1977年 | 12篇 |
1975年 | 13篇 |
1973年 | 10篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
F Febres H Scaglia R Lisker J Espinosa T Morato M Shkurovich G P?rez-Palacios 《The Journal of clinical endocrinology and metabolism》1975,41(5):833-840
Gonadal function was studied in three post-pubertal siblings (two male and one female) and one unrelated male patient with myotonic dystrophy. The diagnosis was confirmed in all cases by electromyography and muscle biopsy. Basal levels of plasma immunoreactive LH, FSH, testosterone, and estradiol were measured. Hypothalamic, pituitary, and gonadal reserve and responsiveness were evaluated by clomiphene, LHRH, and HCG tests. Histologic examination of gonadal biopsies was also performed. The results showed that gonadal failure present in the four patients had different characteristics. In the same family, hypothalamic amenorrhea was observed in the female patient, and hypothalamic eunuchoidism and hypergonadotropic hypogonadism with marked tubular and leydig cells failure in the male patients. The non-related male patient had hypergonadotropic hypogonadism with tubular failure but with a compensatory leydig-cell hyperplasia. These data are interpreted as demonstrating different expressivity of the hypogonadism associated with the same inherited muscle disease. 相似文献
992.
Claudia Lützelschwab Gunnar Pejler Maria Aveskogh Lars Hellman 《The Journal of experimental medicine》1997,185(1):13-30
Two of the major rat mast cell proteases, rat mast cell protease 1 (RMCP-1) and RMCP-2, have for many years served as important phenotypic markers for studies of various aspects of mast cell (MC) biology. However, except for these proteases only fragmentary information has been available on the structure and complexity of proteases expressed by different subpopulations of rat MCs. To address these questions, cDNA libraries were constructed from freshly isolated rat peritoneal MCs and from the rat mucosal MC line RBL-1. cDNA clones for 10 different serine proteases (RMCP-1-10), and the MC carboxypeptidase A were isolated and characterized. Six of these proteases have not been isolated previously. Based on their protease content, three separate subpopulations of MCs were identified. Connective tissue MCs (CTMCs) from the ear and peritoneum express the chymases RMCP-1 and -5, the tryptases RMCP-6, and -7 and the carboxypeptidase A. However, based on a large difference in the level of expression of RMCP-7, CTMCs of these two organs may be regarded as two separate subpopulations. RMCP-2 and the three closely related proteases of the RMCP-8 subfamily were identified as the major mucosal MC proteases in rat. In contrast to what has been reported for human MCs, no expression of cathepsin G or cathepsin G–like proteases was detected in any of the rat MC populations. To determine mRNA frequencies for the various proteases expressed by normal tissue MCs, an unamplified peritoneal MC cDNA library was screened with a panel of monospecific cDNA probes. These results showed that peritoneal MCs are highly specialized effector cells with mRNA frequencies for the major proteases in the range of several percent of the total mRNA pool. 相似文献
993.
Alin Abreu Alejandro Pinzón Tovar Rafael Castellanos Alex Valenzuela Claudia Milena Gómez Giraldo Alejandro Castellanos Pinedo Doly Pantoja Guerrero Carlos Alfonso Builes Barrera Humberto Ignacio Franco Antônio Ribeiro-OliveiraJr. Lucio Vilar Raquel S. Jallad Felipe Gaia Duarte Mônica Gadelha Cesar Luiz Boguszewski Julio Abucham Luciana A. Naves Nina Rosa C. Musolino Maria Estela Justamante de Faria Ciliana Rossato Marcello D. Bronstein 《Pituitary》2016,19(4):448-457
Introduction
Acromegaly is a rare, insidious disease resulting from the overproduction of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), and is associated with a range of comorbidities. The extent of associated complications and mortality risk is related to length of exposure to the excess GH and IGF-1, thus early diagnosis and treatment is imperative. Unfortunately, acromegaly is often diagnosed late, when patients already have a wide range of comorbidities. The presence of comorbid conditions contributes significantly to patient morbidity/mortality and impaired quality of life.Methods
We conducted a retrospective literature review for information relating to the diagnosis of acromegaly, and its associated comorbidities using PubMed. The main aim of this review is to highlight the issues of comorbidities in acromegaly, and to reinforce the importance of early diagnosis and treatment.Findings and conclusions
Successful management of acromegaly goes beyond treating the disease itself, since many patients are diagnosed late in disease evolution, they present with a range of comorbid conditions, such as cardiovascular disease, diabetes, hypertension, and sleep apnea. It is important that patients are screened carefully at diagnosis (and thereafter), for common associated complications, and that biochemical control does not become the only treatment goal. Mortality and morbidities in acromegaly can be reduced successfully if patients are treated using a multimodal approach with comprehensive comorbidity management.994.
Castelli MP Casu A Casti P Lobina C Carai MA Colombo G Solinas M Giunta D Mugnaini C Pasquini S Tafi A Brogi S Gessa GL Corelli F 《The Journal of pharmacology and experimental therapeutics》2012,340(3):529-538
The potential efficacy of GABA(B) receptor agonists in the treatment of pain, drug addiction, epilepsy, cognitive dysfunctions, and anxiety disorders is supported by extensive preclinical and clinical evidence. However, the numerous side effects produced by the GABA(B) receptor agonist baclofen considerably limit the therapeutic use of this compound. The identification of positive allosteric modulators (PAMs) of the GABA(B) receptor may constitute a novel approach in the pharmacological manipulation of the GABA(B) receptor, leading to fewer side effects. The present study reports the identification of two novel compounds, methyl 2-(1-adamantanecarboxamido)-4-ethyl-5-methylthiophene-3-carboxylate (COR627) and methyl 2-(cyclohexanecarboxamido)-4-ethyl-5-methylthiophene-3-carboxylate (COR628), which act as GABA(B) PAMs in 1) rat cortical membranes and 2) in vivo assay. Both compounds potentiated GABA- and baclofen-stimulated guanosine 5'-O-(3-[(35)S]thio)-triphosphate binding to native GABA(B) receptors, while producing no effect when given alone. GABA concentration-response curves in the presence of fixed concentrations of COR627 and COR628 revealed an increase of potency of GABA rather than its maximal efficacy. In radioligand binding experiments [displacement of the GABA(B) receptor antagonist, 3-N-[1-((S)-3,4dichlorophenyl)-ethylaminol]-2-(S)hydroxypropyl cyclo-hexylmethyl phosphinic acid ([(3)H]CGP54626)], both COR627 and COR628 increased the affinity of high- and low-affinity binding sites for GABA, producing no effect when administered alone up to a concentration of 1 mM. In vivo experiments indicated that pretreatment with per se ineffective doses of COR627 and COR628 potentiated the sedative/hypnotic effect of baclofen. In conclusion, COR627 and COR628 may represent two additional tools for use in investigating the roles and functions of positive allosteric modulatory binding sites of the GABA(B) receptor. 相似文献
995.
Kye Hun Kim William R. Miranda Larry J. Sinak Faisal F. Syed Rowlens M. Melduni Raul E. Espinosa Garvan C. Kane Jae K. Oh 《JACC: Cardiovascular Imaging》2018,11(4):534-541
Objectives
This study sought to investigate the incidence, associated findings, and natural history of effusive-constrictive pericarditis (ECP) after pericardiocentesis.Background
ECP is characterized by the coexistence of tense pericardial effusion and constriction of the heart by the visceral pericardium. Echocardiography is currently the main diagnostic tool in the assessment of pericardial disease, but limited data have been published on the incidence and prognosis of ECP diagnosed by echo-Doppler.Methods
A total of 205 consecutive patients undergoing pericardiocentesis at Mayo Clinic, Rochester, Minnesota, were divided into 2 groups (ECP and non-ECP) based on the presence or absence of post-centesis echocardiographic findings of constrictive pericarditis. Clinical, laboratory, and imaging characteristics were compared.Results
ECP was subsequently diagnosed in 33 patients (16%) after pericardiocentesis. Overt clinical cardiac tamponade was present in 52% of ECP patients and 36% of non-ECP patients (p = 0.08). Post-procedure hemopericardium was more frequent in the ECP group (33% vs. 13%; p = 0.003), and a higher percentage of neutrophils and lower percentage of monocytes were noted on pericardial fluid analysis in those patients. Clinical and laboratory findings were otherwise similar. Baseline early diastolic mitral septal annular velocity was significantly higher in the ECP group. Before pericardiocentesis, respiratory variation of mitral inflow velocity, expiratory diastolic flow reversal of hepatic vein, and respirophasic septal shift were significantly more frequent in the ECP group. Fibrinous or loculated effusions were also more frequently observed in the ECP group. Four deaths occurred in the ECP group; all 4 patients had known malignancies. During median follow-up of 3.8 years (interquartile range: 0.5 to 8.3 years), only 2 patients required pericardiectomy for persistent constrictive features and symptoms.Conclusions
In a large cohort of unselected patients undergoing pericardiocentesis, 16% were found to have ECP. Pre-centesis echocardiographic findings might identify such patients. Long-term prognosis in those patients remains good, and pericardiectomy was rarely required. 相似文献996.
Haemodynamic effects of an acute vasodilator challenge in heart failure patients with reduced ejection fraction and different forms of post‐capillary pulmonary hypertension 下载免费PDF全文
Stefano Ghio Gabriele Crimi Pier Luigi Temporelli Egidio Traversi Maria Teresa La Rovere Antonia Cannito Dario Vizza Laura Scelsi Claudia Raineri Marco Guazzi Luigi Oltrona Visconti 《European journal of heart failure》2018,20(4):725-734
Aims
The most recent European guidelines have proposed new definitions of pulmonary hypertension (PH) in left heart disease, to better approach the characteristics required to reflect the presence of pulmonary vascular disease. The purpose of this study was to assess whether different haemodynamic definitions of post‐capillary PH imply a different reversibility of PH in response to acute vasodilator administration in heart failure patients with reduced ejection fraction and PH (HFrEF‐PH).Methods and results
Right heart catheterization and reversibility testing was performed in 156 HFrEF‐PH patients. Patients were classified as combined post‐capillary and pre‐capillary pulmonary hypertension (Cpc‐PH) vs. isolated post‐capillary pulmonary hypertension (Ipc‐PH) and on the basis of diastolic pulmonary gradient (DPG) ≥ 7 vs. < 7 mmHg or of transpulmonary gradient (TPG) >12 vs. ≤12 mmHg. After vasodilator administration, Cpc‐PH patients showed a greater per cent improvement in pulmonary vascular resistance (PVR), DPG and TPG as compared with Ipc‐PH patients (all Pint < 0.001); only pulmonary compliance (PCa) improved less in Cpc‐PH than in Ipc‐PH patients (Pint = 0.007). However, despite vasodilatation, Cpc‐PH patients remained in an unfavourable portion of the inverse hyperbolic relationship between PVR and PCa. The number of patients in whom PVR was reduced below 2.5 wood units was similar in Cpc‐PH, DPG ≥7 mmHg and TPG >12 mmHg groups (28.3, 26.7 and 18.9%, respectively).Conclusion
Although substantial improvements in PVR, DPG and TPG were observed in Cpc‐PH patients after acute vasodilator administration, this response was associated with persistent abnormalities in the PVR vs. PCa relationship. The link between baseline right heart haemodynamics and pulmonary vascular disease remains elusive.997.
Alfonso Berrocal Luis Cabañas Enrique Espinosa Ricardo Fernández-de-Misa Salvador Martín-Algarra José Carlos Martínez-Cedres Luis Ríos-Buceta José Luis Rodríguez-Peralto 《Advances in therapy》2014,31(9):945-960
The incidence of malignant melanoma is increasing worldwide. In Spain, its incidence is increasing faster than any other cancer type, with a 5-year survival rate of about 85%. The impact and characteristics of malignant melanoma in the Spanish population can be ascertained from the national melanoma registry of the Academia Española de Dermatología y Venereología. This review presents consensus group recommendations for the diagnosis, staging and treatment of malignant melanoma in Spain. Incidence and mortality are discussed, as well as evaluation of various prevention and treatment strategies. Prognostic factors, such as BRAF and C-KIT mutations, which are expected to become routine staging procedures over the next few years, are outlined, especially in relation to treatment options. The use of recently approved targeted agents such as ipilimumab, a cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitor, and vemurafenib, a BRAF inhibitor, in metastatic disease are also discussed. 相似文献
998.
Ximena Wortsman MD Fernando Alfageme MD Gaston Roustan MD Salvador Arias-Santiago MD Antonio Martorell MD Orlando Catalano MD Maria Scotto di Santolo MD Kian Zarchi MD Marcio Bouer MD Claudia Gonzalez MD Robert Bard MD Anitha Mandava MD Diana Gaitini MD 《Journal of ultrasound in medicine》2016,35(3):577-580
999.
Frauke Ringel Helge Schoenfeld Said El Bali Jalid Sehouli Claudia Spies Abdulgabar Salama 《Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie》2022,49(4):234
IntroductionUncrossmatched ABO-compatible red blood cells (RBCs) are generally recommended in patients with life-threatening massive bleeding. There is little data regarding RBC transfusion when patients are transfused against clinically significant alloantibodies because compatible RBCs are not immediately available.Methods/PatientsAll patients reviewed in this study (n = 6,109) required emergency blood transfusion and were treated at the Charité − Universitätsmedizin Berlin between 2001 and 2015. Primary uncrossmatched O Rh(D)-positive or -negative RBC units were immediately transfused prior to complete regulatory serological testing including determination of ABO group, Rhesus antigens, antibody screening, and crossmatching.ResultsWithout any significant change in the protocol of emergency transfusion of RBCs, a total of 63,373 RBC units were transfused in 6,109 patients. Antibody screening was positive in 413 patients (6.8%), and 19 of these patients received RBC units against clinically significant alloantibodies. None of these patients appeared to have developed significant hemolysis, and only one patient with anti-D seems to have developed signs of insignificant hemolysis following the transfusion of three Rh(D)-positive units. One patient who had anti-Jka received unselected units and did not develop a hemolytic transfusion reaction.ConclusionTransfusion of uncrossmatched ABO-compatible RBCs against alloantibodies is highly safe in patients with life-threatening hemorrhage. 相似文献
1000.
Baldelli R Battista C Leonetti F Ghiggi MR Ribaudo MC Paoloni A D'Amico E Ferretti E Baratta R Liuzzi A Trischitta V Tamburrano G 《Clinical endocrinology》2003,59(4):492-499
OBJECTIVE: Acromegaly is a syndrome with a high risk of impaired glucose tolerance (IGT) and diabetes mellitus (DM). Somatostatin analogues, which are used for medical treatment of acromegaly, may exert different hormonal effects on glucose homeostasis. Twenty-four active acromegalic patients were studied in order to determine the long-term effects of octreotide-LAR and SR-lanreotide on insulin sensitivity and carbohydrate metabolism. DESIGN: Prospective study. PATIENTS: We studied 24 patients with active acromegaly, 11 males and 13 females, aged 50.7 +/- 12.7 years, body mass index (BMI) 30.1 +/- 4.8 (kg/m2). MEASUREMENTS: All patients underwent an oral glucose tolerance test (OGTT) and 12 also had an euglycaemic hyperinsulinaemic clamp. All patients were evaluated at baseline and after 6 months of somatostatin analogues therapy. RESULTS: Acromegalic patients showed low M-values in respect to the control group at baseline (P<0.05), followed by a significant improvement after 6 months of therapy (P<0.005 vs. baseline). Serum glucose levels at 120 min during OGTT worsened (P<0.05) during somatostatin analogs therapy in patients with normal glucose tolerance, but not in those with impaired glucose tolerance or diabetes mellitus. This was associated with a reduced (P<0.05) and 30 min delayed insulin secretion during OGTT. Also, HbA1c significantly deteriorated in all subjects after treatment (4.7 +/- 0.6% and 5.1 +/- 0.5%, basal and after six months, respectively, P<0.005). CONCLUSION: In acromegalic patients, somatostatin analogues treatment reduces insulin resistance, and also impairs insulin secretion. This may suggest that the use of oral secretagogue hypoglycaemic agents and/or insulin therapy should be considered rather than insulin sensitizers, as the treatment of choice in acromegalic patients who develop frank hyperglycaemia during somatostatin analogues therapy. 相似文献