全文获取类型
收费全文 | 4081篇 |
免费 | 306篇 |
国内免费 | 31篇 |
专业分类
耳鼻咽喉 | 39篇 |
儿科学 | 120篇 |
妇产科学 | 67篇 |
基础医学 | 535篇 |
口腔科学 | 67篇 |
临床医学 | 423篇 |
内科学 | 925篇 |
皮肤病学 | 49篇 |
神经病学 | 381篇 |
特种医学 | 201篇 |
外科学 | 648篇 |
综合类 | 21篇 |
一般理论 | 1篇 |
预防医学 | 212篇 |
眼科学 | 47篇 |
药学 | 358篇 |
中国医学 | 4篇 |
肿瘤学 | 320篇 |
出版年
2023年 | 26篇 |
2022年 | 44篇 |
2021年 | 103篇 |
2020年 | 63篇 |
2019年 | 105篇 |
2018年 | 119篇 |
2017年 | 81篇 |
2016年 | 95篇 |
2015年 | 114篇 |
2014年 | 157篇 |
2013年 | 177篇 |
2012年 | 307篇 |
2011年 | 281篇 |
2010年 | 173篇 |
2009年 | 152篇 |
2008年 | 252篇 |
2007年 | 255篇 |
2006年 | 262篇 |
2005年 | 243篇 |
2004年 | 210篇 |
2003年 | 228篇 |
2002年 | 220篇 |
2001年 | 18篇 |
2000年 | 22篇 |
1999年 | 29篇 |
1998年 | 49篇 |
1997年 | 45篇 |
1996年 | 29篇 |
1995年 | 23篇 |
1994年 | 18篇 |
1993年 | 17篇 |
1992年 | 18篇 |
1991年 | 15篇 |
1990年 | 12篇 |
1989年 | 18篇 |
1988年 | 27篇 |
1986年 | 15篇 |
1985年 | 20篇 |
1984年 | 15篇 |
1983年 | 18篇 |
1981年 | 21篇 |
1980年 | 18篇 |
1978年 | 12篇 |
1977年 | 16篇 |
1976年 | 19篇 |
1975年 | 12篇 |
1973年 | 18篇 |
1965年 | 10篇 |
1964年 | 10篇 |
1960年 | 11篇 |
排序方式: 共有4418条查询结果,搜索用时 15 毫秒
971.
Aracil-Bolaños Ignacio Sampedro Frederic Marín-Lahoz Juan Horta-Barba Andrea Martínez-Horta Saül Gónzalez-de-Echávarri José María Pérez-Pérez Jesús Bejr-Kasem Helena Pascual-Sedano Berta Botí Mariángeles Campolongo Antonia Izquierdo Cristina Gironell Alexandre Gómez-Ansón Beatriz Kulisevsky Jaime Pagonabarraga Javier 《Brain imaging and behavior》2022,16(2):761-772
Brain Imaging and Behavior - Mild cognitive impairment in Parkinson’s disease (PD-MCI) is associated with consistent structural and functional brain changes. Whether different approaches for... 相似文献
972.
François Sevrin Hélène Kolesnikov-Gauthier Olivier Cougnenc Emilie Bogart Gudrun Schleiermacher Frederic Courbon Marion Gambart Anne-Laure Giraudet Nadège Corradini Jean-Noël Badel Erwann Rault Aurore Oudoux Marie Cécile Le Deley Dominique Valteau-Couanet Anne-Sophie Defachelles 《Pediatric blood & cancer》2023,70(11):e30615
Purpose
We report the results of the French multicentric phase II study MIITOP (NCT00960739), which evaluated tandem infusions of 131I-metaiodobenzylguanidine (mIBG) and topotecan in children with relapsed/refractory metastatic neuroblastoma (NBL).Methods
Patients received 131I-mIBG on day 1, with intravenous topotecan daily on days 1–5. A second activity of 131I-mIBG was given on day 21 to deliver a whole-body radiation dose of 4 Gy, combined with a second course of topotecan on days 21–25. Peripheral blood stem cells were infused on day 31.Results
Thirty patients were enrolled from November 2008 to June 2015. Median age at diagnosis was 5.5 years (2–20). Twenty-one had very high-risk NBL (VHR-NBL), that is, stage 4 NBL at diagnosis or at relapse, with insufficient response (i.e., less than a partial response of metastases and more than three mIBG spots) after induction chemotherapy; nine had progressive metastatic relapse. Median Curie score at inclusion was 6 (1–26). Median number of prior lines of treatment was 3 (1–7). Objective response rate was 13% (95% confidence interval [CI]: 4–31) for the whole population, 19% for VHR-NBL, and 0% for progressive relapses. Immediate tolerance was good, with nonhematologic toxicity limited to grade-2 nausea/vomiting in eight patients. Two-year event-free survival was 17% (95% CI: 6–32). Among the 16 patients with VHR-NBL who had not received prior myeloablative busulfan-melphalan consolidation, 13 had at least stable disease after MIITOP; 11 subsequently received busulfan-melphalan; four of them were alive (median follow-up: 7 years).Conclusion
MIITOP showed acceptable tolerability in this heavily pretreated population and encouraging survival rates in VHR-NBL when followed by busulfan-melphalan. 相似文献973.
Cecile Faure-Conter Daniel Orbach Hélène Sudour-Bonnange Cecile Verité Ludovic Mansuy Angelique Rome Cecile Dumesnil Estelle Thebaud Marleen Renard Frederic Hameury Aude Flechon Ellen Blanc Frederique Dijoud Brice Fresneau Sylvie Chabaud 《Pediatric blood & cancer》2023,70(3):e30117
Background
Chemotherapy for non-seminomatous germ cell tumours (NSGCT) exposes to dose-dependent toxicities. The TGM13-NS protocol (EudraCT 2013-004039-60) aimed to decrease the chemotherapy burden compared to the previous TGM95 protocol while maintaining the 5-year event-free survival (EFS) at 80% or more.Procedure
Patients less than 19 years of age with disseminated NSGCT were enrolled (May 2014 to May 2019) and stratified into four groups: two intermediate-risk (IR: localised tumour with low tumour markers [TM]) groups treated with VBP (vinblastine–bleomycin–cisplatin): three courses for IR1 (ovarian tumour any age/testis tumour less than or equal to 10 years) and four courses for IR2 (extragonadal tumour 10 years or less) groups, and two high-risk (HR: metastatic and/or high TM) groups treated with etoposide–cisplatin and either ifosfamide (VIP) or bleomycin (BEP): three courses for HR1 (ovarian tumour any age/testis tumour less than or equal to 10 years and low TM/testis tumour more than 10 years and very low TM) groups and four courses for HR2 (remainder) groups.Results
One hundred fifteen patients were included: median age of 12.8 years (0.4–18.9); tumour sites: 44 ovaries, 37 testes and 34 extragonadal. The 5-year EFS and overall survival (OS) were 87% (95% CI: 80–92) and 95% (89–98), respectively (median follow-up: 3.5 years, range: 0.2–5.9), similar to those of the TGM95 protocol (5-year EFS 89% (84–93), 5-year OS 93% (89–95), p = .561). The 5-year EFS were 93% (95% CI: 80–98), 88% (71–95) and 79% (62–90) for ovarian, testicular and extragonadal tumours, respectively. The 5-year EFS varied (p = .02) according to the risk groups: 90% (66–97), 64% (30–85), 95% (72–99) and 87% (74–94) for IR1, IR2, HR1 and HR2, respectively. TM decline adjusted to tumour site, and alpha-fetoprotein (AFP) level revealed a prognostic impact of time to normalisation on EFS: HR = 1.03 (1.003–1.007).Conclusion
Risk-adapted and globally decreased chemotherapy burden maintains excellent outcomes, exclusive of the IR2 group, which warrants more intensive chemotherapy. 相似文献974.
Merrick EL Hodgkin D Garnick DW Horgan CM Panas L Ryan M Saitz R Blow FC 《Journal of general internal medicine》2008,23(11):1741-1748
Background Preventive service use among older adults is suboptimal. Unhealthy drinking may constitute a risk factor for failure to receive
these services.
Objectives To determine the relationship between unhealthy drinking and receipt of recommended preventive services among elderly Medicare
beneficiaries, applying the framework of current alcohol consumption guidelines.
Design/Methods The data source is the nationally representative 2003 Medicare Current Beneficiary Survey. The sample included community-dwelling,
fee-for-service Medicare beneficiaries 65 years and older (N = 10,523). Based on self-reported drinking, respondents were
categorized as nondrinkers, within-guidelines drinkers, exceeding monthly but not daily limits, or heavy episodic drinkers.
Using survey and claims data, influenza vaccination, pneumonia vaccination, glaucoma screening, and mammogram receipt were
determined. Bivariate and logistic regression analyses were conducted.
Results Overall, 70.3% received flu vaccination and 49% received glaucoma screening during the year, 66.8% received pneumonia vaccination,
and 56.2% of women received a mammogram over 2 years. In logistic regression, heavy episodic drinking was associated with
lower likelihood of service receipt compared to drinking within guidelines: flu vaccination (OR 0.75, CI 0.59–0.96), glaucoma
screening (OR 0.74, CI 0.58–0.95), and pneumonia vaccination (OR 0.75, CI 0.59–0.96). Nondrinkers when compared with those
reporting drinking within guidelines were less likely to receive a mammogram (OR 0.83, CI 0.69–1.00).
Conclusions Heavy episodic drinking is associated with lower likelihood of receiving several preventive services. Practitioners should
be encouraged to screen all elders regarding alcohol intake and in addition to appropriate intervention, consider elders reporting
heavy episodic drinking at higher risk for non-receipt of preventive services. 相似文献
975.
Mycobacterial catalase-peroxidase is a tissue antigen and target of the adaptive immune response in systemic sarcoidosis 总被引:1,自引:0,他引:1 下载免费PDF全文
Song Z Marzilli L Greenlee BM Chen ES Silver RF Askin FB Teirstein AS Zhang Y Cotter RJ Moller DR 《The Journal of experimental medicine》2005,201(5):755-767
Sarcoidosis is a disease of unknown etiology characterized by noncaseating epithelioid granulomas, oligoclonal CD4(+) T cell infiltrates, and immune complex formation. To identify pathogenic antigens relevant to immune-mediated granulomatous inflammation in sarcoidosis, we used a limited proteomics approach to detect tissue antigens that were poorly soluble in neutral detergent and resistant to protease digestion, consistent with the known biochemical properties of granuloma-inducing sarcoidosis tissue extracts. Tissue antigens with these characteristics were detected with immunoglobulin (Ig)G or F(ab')(2) fragments from the sera of sarcoidosis patients in 9 of 12 (75%) sarcoidosis tissues (150-160, 80, or 60-64 kD) but only 3 of 22 (14%) control tissues (all 62-64 kD; P = 0.0006). Matrix-assisted laser desorption/ionization time of flight mass spectrometry identified Mycobacterium tuberculosis catalase-peroxidase (mKatG) as one of these tissue antigens. Protein immunoblotting using anti-mKatG monoclonal antibodies independently confirmed the presence of mKatG in 5 of 9 (55%) sarcoidosis tissues but in none of 14 control tissues (P = 0.0037). IgG antibodies to recombinant mKatG were detected in the sera of 12 of 25 (48%) sarcoidosis patients compared with 0 of 11 (0%) purified protein derivative (PPD)(-) (P = 0.0059) and 4 of 10 (40%) PPD(+) (P = 0.7233) control subjects, suggesting that remnant mycobacterial catalase-peroxidase is one target of the adaptive immune response driving granulomatous inflammation in sarcoidosis. 相似文献
976.
Frederic C. Bartter Robert I. Henkin George T. Bryan 《The Journal of clinical investigation》1968,47(8):1742-1752
Patients with the "non-salt-losing" form of the adrenogenital syndrome were studied before and after suppression of adrenal cortical activity with carbohydrate-active steroids. The response of aldosterone secretion to sodium deprivation was measured; in some patients response to adrenocorticotropic hormone (ACTH) was measured as well.The aldosterone secretion was normal and responded normally to sodium deprivation in all patients studied during suppression with carbohydrate-active steroids. This finding suggests that 21-hydroxylation of progesterone is normal in this syndrome.The sole abnormality in the production of aldosterone in these patients was found to be excessive secretion of aldosterone while they were not receiving suppressive doses of carbohydrate-active steroids. This finding strongly supports the view that the biogenetic pathways through which aldosterone is produced from progesterone are intact in this syndrome.No patient showed hypertension or hypokalemic alkalosis despite very high aldosterone secretion rates. This observation suggests that the hyper-aldosteronism is secondary to a tendency to sodium loss in the patient whose ACTH production is not suppressed.These studies provide additional evidence in support of the hypothesis that the salt-losing and "non-salt-losing" forms of adrenogenital syndrome are genetically and biochemically distinct. 相似文献
977.
Transforming Growth Factor β1, in the Presence of Granulocyte/Macrophage Colony-stimulating Factor and Interleukin 4, Induces Differentiation of Human Peripheral Blood Monocytes into Dendritic Langerhans Cells 下载免费PDF全文
Frederic Geissmann Catherine Prost Jean-Paul Monnet Michel Dy Nicole Brousse Olivier Hermine 《The Journal of experimental medicine》1998,187(6):961-966
Langerhans cells (LCs) are dendritic cells (DCs) that are present in the epidermis, bronchi, and mucosae. Although LCs originate in bone marrow, little is known about their lineage of origin. In this study, we demonstrate that in vitro LCs may originate from monocytes. Adult peripheral blood CD14+ monocytes differentiate into LCs (CD1a+, E-cadherin+, cutaneous lymphocyte-associated antigen+, Birbeck granules+, Lag+) in the presence of granulocyte/macrophage colony-stimulating factor, interleukin 4, and transforming growth factor β1 (TGF-β1). This process occurs with virtually no cell proliferation and is not impaired by 30 Gy irradiation. Selection of monocyte subpopulations is ruled out since monocyte-derived DCs can further differentiate into LCs. Our data suggest that in vivo LC differentiation may be induced peripherally, from a nonproliferating myeloid precursor, i.e., the monocyte, in response to a TGF-β1–rich microenvironment, as found in the skin and epithelia. Therefore, the monocyte may represent a circulating precursor critical to the immune response in vivo. 相似文献
978.
Robert F. Malacoff Frederic O. Finkelstein Vincent T. Andriole 《Antimicrobial agents and chemotherapy》1975,8(5):574-580
The pharmacokinetics of tobramycin and clindamycin were examined in patients undergoing peritoneal dialysis for chronic renal failure. Peak serum levels of tobramycin in functionally anephric patients were less than expected, probably secondary to a larger volume of distribution. Peritoneal dialysis resulted in a significant clearance of tobramycin, with a resultant reduction in serum half-life. The present data suggest that, if bactericidal serum levels of tobramycin are to be maintained in patients undergoing peritoneal dialysis, a parenteral loading dose be administered, followed by either (i) an identical dose every third half-life or (ii) one-half the loading dose every half-life. However, optimal therapy is best achieved by monitoring serum levels to insure appropriate drug dosage. Peak serum levels of clindamycin in functionally anephric patients were approximately twofold greater than those expected in normals after an identical parenteral dose. It is, therefore, recommended that the administered dose of this agent in functionally anephric patients be one-half of that required to produce desired peak serum levels in patients without renal impairment. Peritoneal clearance of clindamycin during dialysis was shown to be essentially zero, indicating that dialysis does not affect clindamycin disposition. 相似文献
979.
Atsushi Mizoguchi Emiko Mizoguchi R. Neal Smith Frederic I. Preffer Atul K. Bhan 《The Journal of experimental medicine》1997,186(10):1749-1756
The role of antibodies (Abs) in the development of chronic colitis in T cell receptor (TCR)-α−/− mice was explored by creating double mutant mice (TCR-α−/− × immunoglobulin (Ig)μ−/−), which lack B cells. TCR-α−/− × Igμ−/− mice spontaneously developed colitis at an earlier age, and the colitis was more severe than in TCR-α−/− mice. Colitis was induced in recombination-activating gene-1 (RAG-1−/−) mice by the transfer of mesenteric lymph node (MLN) cells from TCR-α−/− × Igμ−/− mice. When purified B cells from TCR-α−/− mice were mixed with MLN cells before cell transfer, colitis did not develop in RAG-1−/− mice. Administration of the purified Ig from TCR-α−/− mice and a mixture of monoclonal autoAbs reactive with colonic epithelial cells led to attenuation of colitis in TCR-α−/− × Igμ−/− mice. Apoptotic cells were increased in the colon, MLN, and spleen of TCR-α−/− × Igμ−/− mice as compared to Igμ−/− mice and TCR-α−/− mice. Administration of the purified Ig from TCR-α−/− mice into TCR-α−/− × Igμ−/− mice led to decrease in the number of apoptotic cells. These findings suggest that although B cells are not required for the initiation of colitis, B cells and Igs (autoAbs) can suppress colitis, presumably by affecting the clearance of apoptotic cells. 相似文献
980.
Bottlaender M Dolle F Guenther I Roumenov D Fuseau C Bramoulle Y Curet O Jegham J Pinquier JL George P Valette H 《The Journal of pharmacology and experimental therapeutics》2003,305(2):467-473
Befloxatone is a competitive and reversible inhibitor of monoamine oxidase-A (MAOI-A). The aim of the study was to characterize the in vivo properties of [(11)C]befloxatone and to validate its use as a ligand for the study of MAO-A by positron emission tomography (PET). PET studies were performed in baboons after i.v. injection of [(11)C]befloxatone (551 +/- 70 MBq, i.e.14.9 +/- 1.9 mCi). [(11)C]Befloxatone enters rapidly in the brain with a maximum uptake at 30 min. Brain concentration of the tracer is high in thalamus, striatum, pons and cortical structures (1.5-1.8% of injected dose per 100 ml of tissue), and lower in cerebellum (1.07% injected dose/100 ml). Nonsaturable uptake, obtained after a pretreatment with a high dose of nonlabeled befloxatone (0.4 mg/kg), is very low and represents only 3% of the total uptake. Brain uptake of [(11)C]befloxatone is not altered by a pretreatment of a high dose with lazabemide (0.5 mg/kg i.v.), a selective MAOI-B but is completely blocked by a pretreatment with moclobemide (MAOI-A; 10 mg/kg). This confirms, in vivo, the selectivity of befloxatone for type A MAO. [(11)C]Befloxatone brain radioactivity was displaced by administration of unlabeled befloxatone (30 min after the tracer injection). The displacement of the tracer from its binding sites is dose-dependent, with an ID(50) of 0.02 mg/kg for all studied structures. These results indicate that [(11)C]befloxatone will be an excellent probe for the study of MAO-A in humans using PET. 相似文献