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121.
Mateja Smogavec Maria Gerykova Bujalkova Reinhard Lehner Jürgen Neesen Jana Behunova Gülen Yerlikaya-Schatten Theresa Reischer Reinhard Altmann Denisa Weis Hans-Christoph Duba Franco Laccone 《European journal of human genetics : EJHG》2022,30(4):428
Exome sequencing has been increasingly implemented in prenatal genetic testing for fetuses with morphological abnormalities but normal rapid aneuploidy detection and microarray analysis. We present a retrospective study of 90 fetuses with different abnormal ultrasound findings, in which we employed the singleton exome sequencing (sES; 75 fetuses) or to a lesser extent (15 fetuses) a multigene panel analysis of 6713 genes as a primary tool for the detection of monogenic diseases. The detection rate of pathogenic or likely pathogenic variants in this study was 34.4%. The highest diagnostic rate of 56% was in fetuses with multiple anomalies, followed by cases with skeletal or renal abnormalities (diagnostic rate of 50%, respectively). We report 20 novel disease-causing variants in different known disease-associated genes and new genotype–phenotype associations for the genes KMT2D, MN1, CDK10, and EXOC3L2. Based on our data, we postulate that sES of fetal index cases with a concurrent sampling of parental probes for targeted testing of the origin of detected fetal variants could be a suitable tool to obtain reliable and rapid prenatal results, particularly in situations where a trio analysis is not possible.Subject terms: Genetics research, Disease genetics 相似文献
122.
The purpose of fabric masks in the prevention of the spread of COVID-19 often requires that the masks be worn for extended periods without removal. The management of the conditions in the micro-climate inside the masks is important to keep the wearer comfortable and enhance user compliance. In this study, the effect of mask design and fabric type on the micro-climate was investigated using thermocron iButtons to record the temperature and humidity inside the masks. It was found that the mask style, and its effect on the amount of air incorporated in the micro-climate, had a significant influence on the factors that determine the temperature and humidity levels. In the shaped masks, the impact of the mask design on the results was stronger than the effect of fabric type. In the folded masks that fit snugly around the face, the effect of fabric type was significant, and both fibre composition and fabric structure contributed to the differences in the performance of the three fabrics tested. In the case of the masks with an inserted filter, a significant amount of trapped still air in the fabric layers and the increased mask stiffness had the strongest effect on the temperature and humidity inside the masks. Significant differences were also found in the temperatures recorded in the different time segments, highlighting the importance of conducting comfort evaluations over a long enough time to prevent false interpretations. The results of this study emphasize the importance of considering all the components of mask design, namely style, fibre type, and fabric structure, in the development of masks to enhance user compliance. 相似文献
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Nikhil Sasidharan Marija Sumakovic Mandy Hannemann Jan Hegermann Jana F. Liewald Christian Olendrowitz Sabine Koenig Barth D. Grant Silvio O. Rizzoli Alexander Gottschalk Stefan Eimer 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(46):18944-18949
Neurons secrete neuropeptides from dense core vesicles (DCVs) to modulate neuronal activity. Little is known about how neurons manage to differentially regulate the release of synaptic vesicles (SVs) and DCVs. To analyze this, we screened all Caenorhabditis elegans Rab GTPases and Tre2/Bub2/Cdc16 (TBC) domain containing GTPase-activating proteins (GAPs) for defects in DCV release from C. elegans motoneurons. rab-5 and rab-10 mutants show severe defects in DCV secretion, whereas SV exocytosis is unaffected. We identified TBC-2 and TBC-4 as putative GAPs for RAB-5 and RAB-10, respectively. Multiple Rabs and RabGAPs are typically organized in cascades that confer directionality to membrane-trafficking processes. We show here that the formation of release-competent DCVs requires a reciprocal exclusion cascade coupling RAB-5 and RAB-10, in which each of the two Rabs recruits the other’s GAP molecule. This contributes to a separation of RAB-5 and RAB-10 domains at the Golgi–endosomal interface, which is lost when either of the two GAPs is inactivated. Taken together, our data suggest that RAB-5 and RAB-10 cooperate to locally exclude each other at an essential stage during DCV sorting. 相似文献
125.
Patricia Kaazan Zhi Tan Jana Bednarz Julie Hughes Rachel Grafton Jane M. Andrews 《Internal medicine journal》2020,50(9):1134-1138
Association between tumour necrosis alpha inhibitors and weight gain has been reported. We examined weight change in our cohort of inflammatory bowel disease patients treated with infliximab (IFX) for over 12 months, its associations and financial implications. Two‐thirds of patients gained weight during the course of therapy. The mean change in weight after 12 months of IFX therapy was 3.3 (±6.5) kg. 相似文献
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Alexander Ruesch Jason Yang Samantha Schmitt Deepshikha Acharya Matthew A. Smith Jana M. Kainerstorfer 《Biomedical optics express》2022,13(2):710
In our original published article, we labeled the x-axis in Fig. 1(b) incorrectly [Biomed. Opt. Express 11, 1462 (2020) 10.1364/BOE.386612 [PMC free article] [PubMed] [CrossRef] [Google Scholar]]. The sub-figure reports the importance of features extracted from the waveforms in training a machine learning algorithm to estimate intracranial pressure. This erratum corrects the labels in Fig. 1(b). The discussion and conclusions drawn from this article did not change.Open in a separate windowFig. 1.Results of the regression forest machine learning approach. (a) shows the distribution of the available data. The dashed line marks the maximum ICP level that was fitted for at 30 mmHg. (b) shows the distribution of features used in the regression forest as a percentage of all chosen features in all decision criteria generated. The standard deviation across individual trees is shown as error bars. Nomenclature is according to Table 1. (c) shows the performance of the regression forest by plotting estimated ICP (ICPest) over invasively measured ground truth (ICPinv). The solid line shows the ideal fit, while the dashed lines mark an area of 2 mmHg around the ideal fit. The shaded area shows the confidence interval. (d) graphs the difference between ICPest and ICPinv over ICPinv in a Bland-Altman plot. The dashed lines span a region of 95% of the distribution, corresponding to a standard deviation of 1.96. The histogram on the right of this graph shows the distribution of data points in number of samples. (e) shows a continuous estimate of ICP for NHP 3. The gray line shows the estimated ICP, and the black line the invasively measured ICP. An r2 = 0.92 and a mean squared error MSE = 3.2 mmHg2 were achieved. 相似文献
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Jan Kucera Jana Ruda-Kucerova Filip Zlamal Daniela Kuruczova Zuzana Babinska Josef Tomandl Marie Tomandlova Julie Bienertova-Vasku 《Pharmacological reports : PR》2019,71(4):669-675
BackgroundNeurotrophins, especially brain-derived neurotrophic factor (BDNF) have gained significant therapeutic interest particularly in neurologic and psychiatric disorders and they have been found in human breast milk of mothers who suffered from adverse outcomes in pregnancy. This study tested the hypothesis that oral administration of BDNF/GDNF (glial cell line-derived neurotrophic factor) can exert a biological effect in a rat model of severe neuropathology induced by olfactory bulbectomy (OBX), which exhibits dysregulation of BDNF signaling and impaired blood-brain barrier.MethodsAdult male albino Sprague-Dawley rats underwent the OBX surgery and separate groups of OBX and sham-operated controls received one oral dose of vehicle, BDNF (0.005 mg/kg), GDNF (0.03 mg/kg) or their combination. One week after neurotrophin dosing the rats were sacrificed and BDNF level was assessed by ELISA in the blood serum and cerebrospinal fluid.ResultsA significant decrease of serum BDNF level was found in the OBX model. This alteration was normalized by all types of treatment BDNF, GDNF, or their combination. No influence of sham surgery or treatment was observed in the control rats. BDNF levels in cerebrospinal fluid were below detection limit.ConclusionThis study indicates that oral administration of neurotrophins is able to exert a biological effect in the OBX model. There is a number of potential mechanisms, which remain to be elucidated. 相似文献