全文获取类型
收费全文 | 5632篇 |
免费 | 402篇 |
国内免费 | 21篇 |
专业分类
耳鼻咽喉 | 73篇 |
儿科学 | 115篇 |
妇产科学 | 45篇 |
基础医学 | 730篇 |
口腔科学 | 110篇 |
临床医学 | 602篇 |
内科学 | 1303篇 |
皮肤病学 | 136篇 |
神经病学 | 441篇 |
特种医学 | 365篇 |
外科学 | 832篇 |
综合类 | 27篇 |
一般理论 | 5篇 |
预防医学 | 354篇 |
眼科学 | 210篇 |
药学 | 353篇 |
中国医学 | 5篇 |
肿瘤学 | 349篇 |
出版年
2023年 | 39篇 |
2022年 | 72篇 |
2021年 | 148篇 |
2020年 | 86篇 |
2019年 | 143篇 |
2018年 | 177篇 |
2017年 | 132篇 |
2016年 | 161篇 |
2015年 | 200篇 |
2014年 | 225篇 |
2013年 | 317篇 |
2012年 | 431篇 |
2011年 | 460篇 |
2010年 | 261篇 |
2009年 | 227篇 |
2008年 | 335篇 |
2007年 | 341篇 |
2006年 | 356篇 |
2005年 | 310篇 |
2004年 | 267篇 |
2003年 | 291篇 |
2002年 | 238篇 |
2001年 | 79篇 |
2000年 | 75篇 |
1999年 | 59篇 |
1998年 | 49篇 |
1997年 | 38篇 |
1996年 | 26篇 |
1995年 | 23篇 |
1994年 | 22篇 |
1993年 | 16篇 |
1992年 | 37篇 |
1991年 | 42篇 |
1990年 | 32篇 |
1989年 | 28篇 |
1988年 | 34篇 |
1987年 | 24篇 |
1986年 | 16篇 |
1985年 | 19篇 |
1984年 | 21篇 |
1983年 | 21篇 |
1981年 | 11篇 |
1979年 | 12篇 |
1978年 | 9篇 |
1977年 | 10篇 |
1975年 | 9篇 |
1974年 | 16篇 |
1973年 | 10篇 |
1972年 | 13篇 |
1970年 | 9篇 |
排序方式: 共有6055条查询结果,搜索用时 15 毫秒
141.
Sebastian J. Reinstadler Thomas Stiermaier Johanna Liebetrau Georg Fuernau Charlotte Eitel Suzanne de Waha Steffen Desch Jan-Christian Reil Janine Pöss Bernhard Metzler Christian Lücke Matthias Gutberlet Gerhard Schuler Holger Thiele Ingo Eitel 《JACC: Cardiovascular Imaging》2018,11(3):411-419
Objectives
This study assessed the prognostic significance of remote zone native T1 alterations for the prediction of clinical events in a population with ST-segment elevation myocardial infarction (STEMI) who were treated by primary percutaneous coronary intervention (PPCI) and compared it with conventional markers of infarct severity.Background
The exact role and incremental prognostic relevance of remote myocardium native T1 mapping alterations assessed by cardiac magnetic resonance (CMR) after STEMI remains unclear.Methods
We included 255 consecutive patients with STEMI who were reperfused within 12 h after symptom onset. CMR core laboratory analysis was performed to assess left ventricular (LV) function, standard infarct characteristics, and native T1 values of the remote, noninfarcted myocardium. The primary endpoint was a composite of death, reinfarction, and new congestive heart failure within 6 months (major adverse cardiac events [MACE]).Results
Patients with increased remote zone native T1 values (>1,129 ms) had significantly larger infarcts (p = 0.012), less myocardial salvage (p = 0.002), and more pronounced LV dysfunction (p = 0.011). In multivariable analysis, remote zone native T1 was independently associated with MACE after adjusting for clinical risk factors (p = 0.001) or other CMR variables (p = 0.007). In C-statistics, native T1 of remote myocardium provided incremental prognostic information beyond clinical risk factors, LV ejection fraction, and other markers of infarct severity (all p < 0.05). The addition of remote zone native T1 to a model of prognostic CMR parameters (ejection fraction, infarct size, and myocardial salvage index) led to net reclassification improvement of 0.82 (95% confidence interval: 0.46 to 1.17; p < 0.001) and to an integrated discrimination improvement of 0.07 (95% confidence interval: 0.02 to 0.13; p = 0.01).Conclusions
In STEMI patients treated by PPCI, evaluation of remote zone alterations by quantitative noncontrast T1 mapping provided independent and incremental prognostic information in addition to clinical risk factors and traditional CMR outcome markers. Remote zone alterations may thus represent a novel therapeutic target and a useful parameter for optimized risk stratification. (Effect of Conditioning on Myocardial Damage in STEMI [LIPSIA-COND]; NCT02158468) 相似文献142.
Patrick Hoyer Gustavo de Medeiros Bálint Balázs Nils Norlin Christina Besir Janina Hanne Hans-Georg Kr?usslich Johann Engelhardt Steffen J. Sahl Stefan W. Hell Lars Hufnagel 《Proceedings of the National Academy of Sciences of the United States of America》2016,113(13):3442-3446
We present a plane-scanning RESOLFT [reversible saturable/switchable optical (fluorescence) transitions] light-sheet (LS) nanoscope, which fundamentally overcomes the diffraction barrier in the axial direction via confinement of the fluorescent molecular state to a sheet of subdiffraction thickness around the focal plane. To this end, reversibly switchable fluorophores located right above and below the focal plane are transferred to a nonfluorescent state at each scanning step. LS-RESOLFT nanoscopy offers wide-field 3D imaging of living biological specimens with low light dose and axial resolution far beyond the diffraction barrier. We demonstrate optical sections that are thinner by 5–12-fold compared with their conventional diffraction-limited LS analogs.Far-field nanoscopy (1, 2) methods discern features within subdiffraction distances by briefly forcing their molecules to two distinguishable states for the time period of detection. Typically, fluorophores are switched between a signaling “on” and a nonsignaling (i.e., dark) “off” state. Depending on the switching and fluorescence registration strategy used, these superresolution techniques can be categorized into coordinate-stochastic and coordinate-targeted approaches (2). The latter group of methods, comprising the so-called RESOLFT [reversible saturable/switchable optical (fluorescence) transitions] (1, 3–7) approaches, have been realized using patterns of switch-off light with one or more zero-intensity points or lines, to single out target point (zero-dimensional) or line (1D) coordinates in space where the fluorophores are allowed to assume the on state. The RESOLFT idea can also be implemented in the inverse mode, by using switch-on light and confining the off state. In any case, probing the presence of molecules in new sets of points or lines at every scanning step produces images.Owing to the nature of the on and off states involved––first excited electronic and ground state––stimulated emission depletion (STED) (3) and saturated structured illumination microscopy (SSIM) (8), which both qualify as variants of the RESOLFT principle, typically apply light intensities in the range of MW/cm2 and above. Especially when imaging sensitive samples where photoinduced changes must be avoided, RESOLFT is preferably realized with fluorophores which lead to the same factor of resolution improvement at much lower intensities of state-switching light. Reversibly switchable fluorescent proteins (RSFPs) are highly suitable for this purpose (4–7, 9), as transitions between their metastable on and off states require 5 orders of magnitude lower threshold intensities than STED/SSIM to guarantee switch-off. Suitable spectral properties, relatively fast millisecond switching kinetics, and high photostability of recently developed yellow-green-emitting RSFPs like rsEGFP (5), rsEGFP2 (7), and rsEGFP(N205S) (10) compared with early RSFPs have indeed enabled RESOLFT nanoscopy in living cells and tissues. To date, RSFP-based RESOLFT has achieved resolution improvements by factors of 4–5 in rsEGFP2-labeled samples (7). To further reduce the imaging time, massive parallelization of scanning has been reported (10). However, the diffraction-limited axial resolution and lack of background suppression restrict applications to thin samples.Imaging applications typically require careful tuning of imaging parameters including speed, contrast, photosensitivity, and spatial resolution, depending on the information that is sought. Light-sheet fluorescence microscopy (LSFM) (11–15) stands out by its ability to balance most of these parameters for 3D imaging of living specimens. Recently reenacted as the selective plane illumination microscope (13), this microscopy mode has sparked increasing interest notably because of its short acquisition times in 3D imaging and low phototoxicity in living specimens. It excites fluorophores only in a thin diffraction-limited slice of the sample, perpendicular to the direction of fluorescence detection. The LS is generated by a cylindrical lens which focuses an expanded laser beam in only one direction onto the specimen or into the back-focal plane of an illumination objective. Alternatively, a single beam is quickly moved as a “virtual” LS (16) across a specimen section.In such conventional LSFM imaging, the lateral resolution is determined by the numerical aperture (N.A.) of the detection objective (17), whereas axial resolution is given by the LS thickness, provided the latter is thinner than the axial extent of the point-spread function describing the imaging process from the focal plane of the detecting lens to the camera. In a previous study, the axial resolution of LSFM was pushed to the diffraction limit by using the full aperture of the illumination objective with Gaussian beams; this was carried out for practically useful combinations of N.A. (e.g., 0.8 for both illumination and detection objectives) permissible in light of the geometrical constraints given by the objective lens dimensions (18). High-N.A. illumination comes with short Rayleigh ranges of Gaussian beams, which inherently limit the field of view (FOV) along the direction of illumination. Scanned Bessel beams for diffraction-limited excitation with a virtual LS (19–21) typically offer larger FOVs (22), but side lobes broaden the scanned LS in the axial direction and contribute to phototoxicity outside of the focal plane of detection (20). A more complex approach has used Bessel-beam excitation in combination with structured illumination to obtain near-isotropic (but still diffraction-limited) resolution as measured on fluorescent beads (20), albeit at the cost of acquisition time and reduced contrast due to fluorescence generated by the side lobes. In different work, axial resolution has also been improved about fourfold by acquiring two complementary orthogonal views of the sample using two alternating LSs, followed by computationally fusing image information with a deconvolution incorporating both views (23). LS approaches have also helped suppress out-of-focus background for single-molecule imaging in biological situations (e.g., in ref. 24), including at superresolution (25–27).Slight axial resolution improvement beyond the diffraction barrier has been demonstrated by overlapping a Gaussian excitation LS with a STED LS featuring a zero-intensity plane (28). Due to scattering and possibly additional aberrations caused by the wavelength difference between excitation and STED light, the maximal achievable resolution in biological specimens was severely limited. This was the case even in fixed samples. A successful application of LS-STED to living cells or organisms has not been reported. The relatively high average STED laser power required for high resolution gains calls for developing a coordinate-targeted superresolution LS approach with low-power operation, meaning a concept that does not solely rely on changing the way the light is directed to––or collected from––the sample, but a concept that harnesses an “on–off” transition for improved feature separation. 相似文献
143.
144.
145.
Health problems after travel to developing countries 总被引:30,自引:0,他引:30
R Steffen M Rickenbach U Wilhelm A Helminger M Sch?r 《The Journal of infectious diseases》1987,156(1):84-91
Travelers to developing countries participated in a follow-up study of the health risks associated with short (less than three months) visits to these nations. Travelers to the Greek or Canary Islands served as a control cohort. Participants completed a questionnaire to elicit information regarding pretravel vaccinations, malaria prophylaxis, and health problems during and after their journey. Relevant infections were confirmed by the respondent's personal physician. The questionnaire was completed by 10,524 travelers; the answer rate was 73.8%. After a visit to developing countries, 15% of the travelers reported health problems, 8% consulted a doctor, and 3% were unable to work for an average of 15 days. The incidence of infection per month abroad was as follows: giardiasis, 7/1,000; amebiasis, 4/1,000; hepatitis, 4/1,000; gonorrhea, 3/1,000; and malaria, helminthiases, or syphilis, less than 1/1,000. There were no cases of typhoid fever or cholera. 相似文献
146.
147.
Bartsch S Monnet J Selbach K Quigley F Gray J von Wettstein D Reinbothe S Reinbothe C 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(12):4933-4938
Thioredoxins (Trxs) are ubiquitous small proteins with a redox-active disulfide bridge. In their reduced form, they constitute very efficient protein disulfide oxidoreductases. In chloroplasts, two types of Trxs (f and m) coexist and play central roles in the regulation of the Calvin cycle and other processes. Here, we identified a class of Trx targets in the inner plastid envelope membrane of chloroplasts that share a CxxC motif approximately 73 aa from their carboxyl-terminal end. Members of this group belong to a superfamily of Rieske iron-sulfur proteins involved in protein translocation and chlorophyll metabolism. These proteins include the protein translocon protein TIC55, the precursor NADPH:protochlorophyllide oxidoreductase translocon protein PTC52, which operates as protochlorophyllide a-oxygenase, and the lethal leaf spot protein LLS1, which is identical with pheophorbide a oxygenase. The role of these proteins in dark/light regulation and oxidative control by the Trx system is discussed. 相似文献
148.
Steffen Wildum Holger Zimmermann Peter Lischka 《Antimicrobial agents and chemotherapy》2015,59(6):3140-3148
Despite modern prevention and treatment strategies, human cytomegalovirus (HCMV) remains a common opportunistic pathogen associated with serious morbidity and mortality in immunocompromised individuals, such as transplant recipients and AIDS patients. All drugs currently licensed for the treatment of HCMV infection target the viral DNA polymerase and are associated with severe toxicity issues and the emergence of drug resistance. Letermovir (AIC246, MK-8228) is a new anti-HCMV agent in clinical development that acts via a novel mode of action and has demonstrated anti-HCMV activity in vitro and in vivo. For the future, drug combination therapies, including letermovir, might be indicated under special medical conditions, such as the emergence of multidrug-resistant virus strains in transplant recipients or in HCMV-HIV-coinfected patients. Accordingly, knowledge of the compatibility of letermovir with other HCMV or HIV antivirals is of medical importance. Here, we evaluated the inhibition of HCMV replication by letermovir in combination with all currently approved HCMV antivirals using cell culture checkerboard assays. In addition, the effects of letermovir on the antiviral activities of selected HIV drugs, and vice versa, were analyzed. Using two different mathematical techniques to analyze the experimental data, (i) additive effects were observed for the combination of letermovir with anti-HCMV drugs and (ii) no interaction was found between letermovir and anti-HIV drugs. Since none of the tested drug combinations significantly antagonized letermovir efficacy (or vice versa), our findings suggest that letermovir may offer the potential for combination therapy with the tested HCMV and HIV drugs. 相似文献
149.
Brian T. Steffen Lyn M. Steffen Xia Zhou Pamela Ouyang Natalie L. Weir Michael Y. Tsai 《Diabetes care》2015,38(4):575-580
OBJECTIVE
Chronically high nonesterified fatty acids (NEFAs) are a marker of metabolic dysfunction and likely increase risk of type 2 diabetes. By comparison, n-3 fatty acids (FAs) have been shown to have various health benefits and may protect against disease development. In 5,697 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), we examined whether serum levels of NEFAs relate to risk of incident type 2 diabetes and further tested whether plasma n-3 FA levels may interact with this relation.RESEARCH DESIGN AND METHODS
NEFAs were measured in fasting serum using an enzymatic colorimetric assay and phospholipid n-3 FAs eicosapentaenoic and docosahexaenoic acids were determined in plasma through gas chromatography-flame ionization detection in 5,697 MESA participants. Cox proportional hazards regression evaluated the association between NEFA levels and incident type 2 diabetes and whether plasma n-3 FAs modified this association adjusting for age, sex, race, education, field center, smoking, and alcohol use.RESULTS
Over a mean 11.4 years of the study period, higher diabetes incidence was found across successive NEFA quartiles (Q) (hazard ratio [95% CI]): Q1, 1.0; Q2, 1.35 (1.07, 1.71); Q3, 1.58 (1.24, 2.00); and Q4, 1.86 (1.45, 2.38) (Ptrend < 0.001). A significant interaction of n-3 FAs on the relation between NEFAs and type 2 diabetes was also observed (Pinteraction = 0.03). For individuals with lower n-3 levels (<75th percentile), a higher risk of type 2 diabetes was observed across quartiles of NEFAs: Q1, 1.0; Q2, 1.41 (1.07, 1.84); Q3, 1.77 (1.35, 2.31); and Q4, 2.18 (1.65, 2.88) (Ptrend < 0.001). No significant associations were observed in those with n-3 FAs ≥75th percentile (Ptrend = 0.54).CONCLUSIONS
NEFAs are a marker of type 2 diabetes and may have clinical utility for detecting risk of its development. The modifying influence of n-3 FAs suggests a protective effect against disease and/or metabolic dysfunction related to NEFAs and requires further study. 相似文献150.
Kreitschmann-Andermahr Ilonka Siegel Sonja Unger Nicole Streetz-van der Werf Christine Karges Wolfram Schilbach Katharina Schröder Bernadette Szybowicz Janine Sauerwald Janina Zopf Kathrin Grzywotz Agnieszka Bidlingmaier Martin Sommer Heide Strasburger Christian J. 《Pituitary》2020,23(5):479-487
Pituitary - While reasons for non-adherence in children requiring growth hormone (GH) replacement (GH-Rx) are well researched, few studies have investigated adherence in adult GH deficient... 相似文献