全文获取类型
收费全文 | 5773篇 |
免费 | 347篇 |
国内免费 | 33篇 |
专业分类
耳鼻咽喉 | 135篇 |
儿科学 | 189篇 |
妇产科学 | 174篇 |
基础医学 | 988篇 |
口腔科学 | 61篇 |
临床医学 | 449篇 |
内科学 | 1267篇 |
皮肤病学 | 163篇 |
神经病学 | 574篇 |
特种医学 | 76篇 |
外科学 | 453篇 |
综合类 | 31篇 |
一般理论 | 1篇 |
预防医学 | 493篇 |
眼科学 | 99篇 |
药学 | 623篇 |
中国医学 | 13篇 |
肿瘤学 | 364篇 |
出版年
2023年 | 47篇 |
2022年 | 213篇 |
2021年 | 386篇 |
2020年 | 147篇 |
2019年 | 200篇 |
2018年 | 200篇 |
2017年 | 186篇 |
2016年 | 200篇 |
2015年 | 221篇 |
2014年 | 253篇 |
2013年 | 350篇 |
2012年 | 526篇 |
2011年 | 547篇 |
2010年 | 272篇 |
2009年 | 212篇 |
2008年 | 324篇 |
2007年 | 336篇 |
2006年 | 349篇 |
2005年 | 281篇 |
2004年 | 245篇 |
2003年 | 219篇 |
2002年 | 205篇 |
2001年 | 21篇 |
2000年 | 9篇 |
1999年 | 17篇 |
1998年 | 23篇 |
1997年 | 17篇 |
1996年 | 22篇 |
1995年 | 12篇 |
1994年 | 17篇 |
1993年 | 4篇 |
1992年 | 7篇 |
1991年 | 3篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1985年 | 3篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1975年 | 5篇 |
1974年 | 5篇 |
1972年 | 5篇 |
1971年 | 9篇 |
1970年 | 2篇 |
1968年 | 2篇 |
1967年 | 4篇 |
1965年 | 3篇 |
1964年 | 2篇 |
1963年 | 2篇 |
排序方式: 共有6153条查询结果,搜索用时 15 毫秒
141.
Valentin Zumstein Marko Kraljević Annemarie Conzen Sebastian Hoechel Magdalena Müller-Gerbl 《Surgical and radiologic anatomy : SRA》2014,36(4):327-331
Purpose
Among late signs like sclerosis, cysts and osteophytes, alteration of cartilage is a common problem in osteoarthritis. To detect abnormal states in the glenohumeral joint, the physiologic distribution of the cartilage thickness must be known, which will allow physicians to better advise patients. High-resolution computed tomography (CT) data in soft tissue kernel provide highly accurate quantitative results and are a useful method to determine the geometrical situation of the glenohumeral joint. The objective of this study was to characterize the distribution of the thickness of the glenohumeral joint cartilage using CT.Methods
To investigate the distribution of thickness of the joint cartilage, CT images in soft tissue kernel of nine specimens were analyzed using image visualization software. Statistical analysis of the obtained data was performed using the ANOVA test.Results
Results showed different patterns in the glenoid cavity than in humeral head. Cartilage thickness in all glenoids showed maxima in the inferior and anterior portion, whereas central areas are covered with the thinnest cartilage layer. Maximum cartilage thickness in the humeral head was found in the central and superior parts.Conclusion
We could show that the distribution of cartilage thickness in the glenohumeral joint is not homogenous and that there exist several reproducible patterns. Evaluation of cartilage thickness in the glenohumeral joint is of high interest in basic and clinical research. 相似文献142.
Antitumor Effects of Recombinant Antivascular Protein ABRaA-VEGF121 Combined with IL-12 Gene Therapy
Agnieszka Ciomber Andrzej Smagur Iwona Mitrus Tomasz Cichoń Ryszard Smolarczyk Aleksander Sochanik Stanisław Szala Magdalena Jarosz 《Archivum immunologiae et therapiae experimentalis》2014,62(2):161-168
Development and neoplastic progression strongly rely on tumor microenvironment cells. Various kinds of cells that form such tumor milieu play substantial roles in angiogenesis and immunosuppression. Attempts to inhibit tumor vascularization alter tumor milieu and enhance immune response against the tumor. Anticancer therapeutic strategy bringing together antiangiogenic and immunostimulating agents has emerged as a promising approach. We here investigated whether therapy directed against preexisting vessels, combined with an immunomodulatory factor would be equally effective in arresting tumor growth. To this goal, we investigated the effectiveness of ABRaA-vascular endothelial growth factor isoform 121 (VEGF121), an antivascular drug constructed by us. It is a fusion protein composed of VEGF121, and abrin A chain (translation-inhibiting toxin). We used it in combination with interleukin (IL-12) gene therapy and tried to inhibit B16-F10 melanoma tumor growth. ABRaA-VEGF121 is a chimeric recombinant protein capable of destroying tumor vasculature and triggering necrosis in the vicinity of damaged vessels. IL-12 cytokine, in turn, activates both specific and non-specific immune responses. Our results demonstrate that combination of ABRaA-VEGF121 antivascular agent with immunostimulatory cytokine IL-12 indeed inhibits tumor growth more effectively than either agent alone, leading to complete cure of ca. 20 % mice. Post-therapeutic analysis of tumors excised from mice treated with combination therapy showed decreased numbers of blood microvessels in the tumor microenvironment, lowered numbers of regulatory T lymphocytes, as well as showed higher levels of CD4+ and CD8+ as compared to control mice. It seems that bringing together antivascular strategy and the action of immunostimulating agents indeed inhibits growth of tumors. 相似文献
143.
Jonas Pick Aditya Arra Holger Lingel J. Kolja Hegel Magdalena Huber Gopala Nishanth Gerhard Jorch Klaus‐Dieter Fischer Dirk Schlüter Kerry Tedford Monika C. Brunner‐Weinzierl 《European journal of immunology》2014,44(7):2139-2152
Although CD8+ T cells that produce IL‐17 (Tc17 cells) have been linked to host defense, Tc17 cells show reduced cytotoxic activity, which is the characteristic function of CD8+ T cells. Here, we show that CTLA‐4 enhances the frequency of IL‐17 in CD8+ T cells, indicating that CTLA‐4 (CD152) specifically promotes Tc17 differentiation. Simultaneous stimulation of CTLA‐4+/+ and CTLA‐4?/? T cells in cocultures and agonistic CTLA‐4 stimulation unambiguously revealed a cell‐intrinsic mechanism for IL‐17 control by CTLA‐4. The quality of CTLA‐4‐induced Tc17 cells was tested in vivo, utilizing infection with the facultative intracellular bacterium Listeria monocytogenes (LM). Unlike CTLA‐4+/+ Tc17 cells, CTLA‐4?/? were nearly as efficient as Tc1 CTLA‐4+/+ cells in LM clearance. Additionally, adoptively transferred CTLA‐4?/? Tc17 cells expressed granzyme B after rechallenge, and produced Tc1 cytokines such as IFN‐γ and TNF‐α, which strongly correlate with bacterial clearance. CTLA‐4+/+ Tc17 cells demonstrated a high‐quality Tc17 differentiation program ex vivo, which was also evident in isolated IL‐17‐secreting Tc17 cells, with CTLA‐4‐mediated enhanced upregulation of Tc17‐related molecules such as IL‐17A, RORγt, and IRF‐4. Our results show that CTLA‐4 promotes Tc17 differentiation that results in robust Tc17 responses. Its inactivation might therefore represent a central therapeutic target to enhance clearance of infection. 相似文献
144.
Daniel Trujillano Belén Perez Justo González Cristian Tornador Rosa Navarrete Georgia Escaramis Stephan Ossowski Lluís Armengol Verónica Cornejo Lourdes R Desviat Magdalena Ugarte Xavier Estivill 《European journal of human genetics : EJHG》2014,22(4):528-534
Genetic diagnostics of phenylketonuria (PKU) and tetrahydrobiopterin (BH4) deficient hyperphenylalaninemia (BH4DH) rely on methods that scan for known mutations or on laborious molecular tools that use Sanger sequencing. We have implemented a novel and much more efficient strategy based on high-throughput multiplex-targeted resequencing of four genes (PAH, GCH1, PTS, and QDPR) that, when affected by loss-of-function mutations, cause PKU and BH4DH. We have validated this approach in a cohort of 95 samples with the previously known PAH, GCH1, PTS, and QDPR mutations and one control sample. Pooled barcoded DNA libraries were enriched using a custom NimbleGen SeqCap EZ Choice array and sequenced using a HiSeq2000 sequencer. The combination of several robust bioinformatics tools allowed us to detect all known pathogenic mutations (point mutations, short insertions/deletions, and large genomic rearrangements) in the 95 samples, without detecting spurious calls in these genes in the control sample. We then used the same capture assay in a discovery cohort of 11 uncharacterized HPA patients using a MiSeq sequencer. In addition, we report the precise characterization of the breakpoints of four genomic rearrangements in PAH, including a novel deletion of 899 bp in intron 3. Our study is a proof-of-principle that high-throughput-targeted resequencing is ready to substitute classical molecular methods to perform differential genetic diagnosis of hyperphenylalaninemias, allowing the establishment of specifically tailored treatments a few days after birth. 相似文献
145.
Agnieszka Zagrska Anna Partyka Adam Bucki Marcin Koaczkowski Magdalena Jastrzbska‐Wisek Anna Czopek Agata Siwek Monika Guch‐Lutwin Marek Bednarski Marek Bajda Jakub Joczyk Kamil Piska Paulina Koczurkiewicz Anna Wesoowska Maciej Pawowski 《Chemical biology & drug design》2019,93(4):511-521
A series of 2‐pyrimidinyl‐piperazinyl‐alkyl derivatives of 1H‐imidazo[2,1‐f]purine‐2,4(3H,8H)‐dione has been synthesized in an attempt to discover a new class of psychotropic agents. Compounds were evaluated for their in vitro affinity for serotonin 5‐HT1A, 5‐HT7, and phosphodiesterases PDE4 and PDE10. The most potent compound 2‐pyrimidinyl‐1‐piperazinyl‐butyl‐imidazo[2,1‐f]purine‐2,4‐dione ( 4b ) behaved as strong and selective antagonist of 5‐HT1A. Molecular modeling studies revealed differences in binding mode between compound 4b and buspirone, which might reflect variation of the ligands’ affinity and potency in the 5‐HT1A receptor. Compound 4b in silico models demonstrated drug‐likeness properties and, contrary to buspirone, showed a metabolic stability in mouse liver microsomes system. Experimentally obtained value of apparent permeability coefficient Papp for 4b in parallel artificial permeability assay indicates the possibility of binding weakly to plasma proteins and high intestinal absorption fraction. Evaluation of the antidepressant‐ and anxiolytic‐like activities of 4b revealed both activities at the same dose of 1.25 mg/kg and seemed to be specific. The antidepressant and/or anxiolytic properties of 4b may be related to its first‐pass effect. 相似文献
146.
Margarita Gutirrez Gabriel A. Vallejos Magdalena P. Corts Carlos Bustos 《Chemical biology & drug design》2019,93(6):1117-1128
In recent years, the design, development, and evaluation of several inhibitors of the BACE1 enzyme, as part of Alzheimer's treatment, have gathered the scientific community's interest. Here, a linear regression model was built using binding free energy calculations through the Bennett acceptance ratio method for 20 known inhibitors of the BACE1 enzyme, with a Pearson coefficient of R = 0.88 and R2 = 0.78. The validation of this model was verified employing eight additional random inhibitors, which also gave a linear correlation with R = 0.97 and R2 = 0.93. Furthermore, this linear regression model was also used for proposing the structure of four potential BACE1 inhibitors, and the most active of them gave a theoretical Kd = 10 nM. However, these molecules have not been synthesized yet. Our team used a total time of more than 800 ns for the Molecular Dynamics to carry out this study, and all the software used were freely available. 相似文献
147.
148.
Jason B. Luoma Magdalena Kulesza Steven C. Hayes Barbara Kohlenberg Mary Larimer 《The American journal of drug and alcohol abuse》2014,40(3):206-212
Background: Stigma has been suggested as a possible contributor to the high rates of treatment attrition in substance-dependent individuals, but no published empirical studies have examined this association. Objectives: The present paper assessed the relationship between baseline stigma variables and length of treatment stay in a sample of patients in a residential addictions treatment unit. Methods: The relationship between baseline stigma variables (self-stigma, enacted stigma, and shame) and length of stay for participants (n?=?103) in a residential addictions treatment unit was examined. Results: Higher self-stigma predicted longer stay in residential addictions treatment, even after controlling for age, marital status, race, overall mental health, social support, enacted stigma, and internalized shame. However, other stigma variables (i.e. internalized shame, stigma-related rejection) did not reliably predict length of treatment stay. Conclusion: These results are consistent with other findings suggesting that people with higher self-stigma may have a lowered sense of self-efficacy and heightened fear of being stigmatized and therefore retreat into more protected settings such as residential treatment, potentially resulting in higher treatment costs. Specialized clinical interventions may be necessary to help participants cope with reduced self-efficacy and fear of being stigmatized. 相似文献
149.
Hendrik Ruge Magdalena Erlebach Eveline Lieberknecht Rüdiger Lange 《Catheterization and cardiovascular interventions》2020,95(4):859-862
Transcatheter heart valve implantation into degenerated bioprosthetic valves (ViV‐THV implantation) has become an established procedure for high risk patients. In general, paravalvular leak (PVL) is a contraindication for valve‐in‐valve‐TAVR (ViV‐TAVR). Herein, we report on a 81‐year‐old patient presenting with acute heart failure for a failing aortic bioprosthesis (Medtronic Mosaic 27 mm). Intraoperative transesophageal echocardiography during urgent ViV‐TAVR revealed a PVL previously not detected. After transfemoral implantation of a 26 mm‐Evolut‐R, balloon‐fracturing of the bioprosthetic ring was performed using a 24 mm True Dilatation balloon for treatment of the PVL. Afterward, left ventricular to aortic peak‐to‐peak pressure gradient measured 2–4mmHg. Transesophageal echocardiography merely revealed trace PVL. Aortic root angiography showed no PVL. At discharge, echocardiography measured a transprosthetic mean gradient of 5mmHg detecting no PVL. Intentional ring‐fracturing of an aortic valve prostheses may prove not only to be effective in lowering transvalvular gradients after valve‐in‐valve‐TAVR, but may also be a tool to treat PVL alongside degenerated surgical aortic bioprostheses in certain patients. 相似文献
150.