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991.
Bryce A. Schuler A. Christian Habermann Erin J. Plosa Chase J. Taylor Christopher Jetter Nicholas M. Negretti Meghan E. Kapp John T. Benjamin Peter Gulleman David S. Nichols Lior Z. Braunstein Alice Hackett Michael Koval Susan H. Guttentag Timothy S. Blackwell Steven A. Webber Nicholas E. Banovich Vanderbilt COVID- Consortium Cohort Human Cell Atlas Biological Network Jonathan A. Kropski Jennifer M.S. Sucre 《The Journal of clinical investigation》2021,131(1)
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) novel coronavirus 2019 (COVID-19) global pandemic has led to millions of cases and hundreds of thousands of deaths. While older adults appear at high risk for severe disease, hospitalizations and deaths due to SARS-CoV-2 among children have been relatively rare. Integrating single-cell RNA sequencing (scRNA-seq) of developing mouse lung with temporally resolved immunofluorescence in mouse and human lung tissue, we found that expression of SARS-CoV-2 Spike protein primer TMPRSS2 was highest in ciliated cells and type I alveolar epithelial cells (AT1), and TMPRSS2 expression increased with aging in mice and humans. Analysis of autopsy tissue from fatal COVID-19 cases detected SARS-CoV-2 RNA most frequently in ciliated and secretory cells in airway epithelium and AT1 cells in peripheral lung. SARS-CoV-2 RNA was highly colocalized in cells expressing TMPRSS2. Together, these data demonstrate the cellular spectrum infected by SARS-CoV-2 in lung epithelium and suggest that developmental regulation of TMPRSS2 may underlie the relative protection of infants and children from severe respiratory illness. 相似文献
992.
993.
Yi Wang Adelaide Bernard Fanny Comblain Xinyu Yue Christophe Paillart Sumei Zhang Jeremy F. Reiter Christian Vaisse 《The Journal of clinical investigation》2021,131(9)
The melanocortin 4 receptor (MC4R) plays a critical role in the long-term regulation of energy homeostasis, and mutations in the MC4R are the most common cause of monogenic obesity. However, the precise molecular and cellular mechanisms underlying the maintenance of energy balance within MC4R-expressing neurons are unknown. We recently reported that the MC4R localizes to the primary cilium, a cellular organelle that allows for partitioning of incoming cellular signals, raising the question of whether the MC4R functions in this organelle. Here, using mouse genetic approaches, we found that cilia were required specifically on MC4R-expressing neurons for the control of energy homeostasis. Moreover, these cilia were critical for pharmacological activators of the MC4R to exert an anorexigenic effect. The MC4R is expressed in multiple brain regions. Using targeted deletion of primary cilia, we found that cilia in the paraventricular nucleus of the hypothalamus (PVN) were essential to restrict food intake. MC4R activation increased adenylyl cyclase (AC) activity. As with the removal of cilia, inhibition of AC activity in the cilia of MC4R-expressing neurons of the PVN caused hyperphagia and obesity. Thus, the MC4R signaled via PVN neuron cilia to control food intake and body weight. We propose that defects in ciliary localization of the MC4R cause obesity in human inherited obesity syndromes and ciliopathies. 相似文献
994.
995.
Christian Bjerregård Øland Søren Wengel Mogensen Amabelia Rodrigues Christine S. Benn Peter Aaby 《Clinical therapeutics》2021,43(1):172-184.e7
PurposeThe diphtheria-tetanus-pertussis vaccine (DTP) and oral polio vaccine (OPV) were introduced in children 3 of 5 months of age in 1981–1983 in Bandim, in the capital of Guinea-Bissau. Because DTP has been linked to deleterious nonspecific effects (NSEs) and OPV to beneficial NSEs, we followed up this cohort to 3 years of age and examined the effects of DTP with OPV on all-cause mortality and the interactions of DTP and OPV with the measles vaccine (MV).MethodsDTP and OPV were offered at 3 monthly community weighing sessions. Vaccination groups were defined by the last vaccine received. We compared overall mortality for different groups in Cox proportional hazards regression models, reporting hazards ratios (HRs) with 95% CIs.FindingsThe study cohort included 1491 children born in Bandim from December 1980 to December 1983. From 3 to 35 months of age, with censoring for MV, children vaccinated with DTP and/or OPV had higher mortality than both unvaccinated children (HR = l.66; 95% CI, 1.03–2.69) and OPV-only vaccinated children (HR = 2.81; 95% CI, 1.02–7.69); DTP-only vaccinated children had higher mortality than OPV-only vaccinated children (HR = 3.38; 95% CI, 1.15-–9.93). In the age group of 3–8 months, before MV is administered, DTP-only vaccination was associated with a higher mortality than DTP with OPV (HR = 3.38; 95% CI, 1.59–7.20). Between 9 and 35 months of age, when MV is given, DTP-vaccinated and MV-unvaccinated children had higher mortality (HR = 2.76; 95% CI, 1.36–5.59) than children who had received MV after DTP, and among children who received DTP with MV or after MV, DTP-only vaccination was associated with a higher mortality than DTP with OPV (HR = 6.25; 95% CI, 2.55–15.37).ImplicationsBecause the 2 vaccines had differential effects and the healthiest children were vaccinated first, selection biases are unlikely to explain the estimated impact on child survival. OPV had beneficial NSEs, and administration of OPV with DTP may have reduced the negative effects of DTP. 相似文献
996.
Jean-Bastien Bott Brigitte Cosquer Céline Héraud Celina Zerbinatti Christian Kelche Jean-Christophe Cassel Chantal Mathis 《Neurobiology of aging》2013
Mild cognitive impairment (MCI) is a clinical condition that often precedes Alzheimer disease (AD). Compared with apolipoprotein E-ε3 (APOE3), the apolipoprotein E-ε4 (APOE4) allele is associated with an increased risk of developing MCI and spatial navigation impairments. In MCI, the entorhinal cortex (EC), which is the main innervation source of the dentate gyrus, displays partial neuronal loss. We show that bilateral partial EC lesions lead to marked spatial memory deficits and reduced synaptic density in the dentate gyrus of APOE4 mice compared with APOE3 mice. Genotype and lesion status did not affect the performance in non-navigational tasks. Thus, partial EC lesions in APOE4 mice were sufficient to induce severe spatial memory impairments and synaptic loss in the dentate gyrus. In addition, lesioned APOE4 mice showed no evidence of reactional increase in cholinergic terminals density as opposed to APOE3 mice, suggesting that APOE4 interferes with the ability of the cholinergic system to respond to EC input loss. These findings provide a possible mechanism underlying the aggravating effect of APOE4 on the cognitive outcome of MCI patients. 相似文献
997.
Christian Schiller Johanna E. HuberKalliope N. Diakopoulos Elisabeth H. Weiss 《Human immunology》2013
Carefully orchestrated intercellular communication is an essential prerequisite for an effective immune response. In recent years tunneling nanotubes (TNT) have emerged as a novel mechanism of cell–cell communication. These long membrane protrusions can establish cytoplasmic continuity between distant cells and enable the exchange of cellular components. In the present study we addressed the question whether these structures can facilitate the intercellular transfer of MHC class I molecules. We found a transmembrane HLA-A2-EGFP but not a soluble HLA-G1s-EGFP fusion protein to be effectively transferred between HeLa cells. Inhibition of actin polymerization significantly reduced the HLA-A2 transfer rate, indicating that transfer is dependent on tunneling nanotubes, whose de novo formation requires actin polymerization. Furthermore, overexpression of the nanotube-inducing protein LST1 promoted transfer of HLA-A2. Moreover, LST1 protein expression is enhanced in antigen presenting cells. Our results indicate that tunneling nanotubes can mediate transfer of MHC class I molecules between distant cells. 相似文献
998.
Theresa Förg Christian T. Mayer Abdul Mannan Baru Catharina Arnold‐Schrauf Wendy W. J. Unger Hakan Kalay Yvette van Kooyk Tim Sparwasser 《European journal of immunology》2013,43(10):2543-2553
Vaccination is one of the oldest yet still most effective methods to prevent infectious diseases. However, eradication of intracellular pathogens and treatment of certain diseases like cancer requiring efficient cytotoxic immune responses remain a medical challenge. In mice, a successful approach to induce strong cytotoxic CD8+ T‐cell (CTL) reactions is to target antigens to DCs using specific antibodies against surface receptors in combination with adjuvants. A major drawback for translating this strategy into one for the clinic is the lack of analogous targets in human DCs. DC‐SIGN (DC‐specific‐ICAM3‐grabbing‐nonintegrin/CD209) is a C‐type lectin receptor with potent endocytic capacity and a highly restricted expression on human immature DCs. Therefore, DC‐SIGN represents an ideal candidate for DC targeting. Using transgenic mice that express human DC‐SIGN under the control of the murine CD11c promoter (hSIGN mice), we explored the efficacy of anti‐DC‐SIGN antibodies to target antigens to DCs and induce protective immune responses in vivo. We show that anti‐DC‐SIGN antibodies conjugated to OVA induced strong and persistent antigen‐specific CD4+ and CD8+ T‐cell responses, which efficiently protected from infection with OVA‐expressing Listeria monocytogenes. Thus, we propose DC targeting via DC‐SIGN as a promising strategy for novel vaccination protocols against intracellular pathogens. 相似文献
999.
Martin Schmid Helga Prettenthaler Christian Weger Karl-Heinz Smolle 《Computers in biology and medicine》2013,43(10):1583-1589
In mechanically ventilated patients, Pulse Pressure Variation (PPV) has been shown to be a useful parameter to guide fluid management. We evaluated a real-time automated PPV-algorithm by comparing it to manually calculated PPV-values. In 10 critically ill patients, blood pressure was measured invasively (IBP) and non-invasively (CNAP® Monitor, CNSystems Medizintechnik, Austria). PPV was determined manually and compared to automated PPV values: PPVmanIBP vs. PPVautoIBP was ?0.19±1.65% (mean bias±standard deviation), PPVmanCNAP vs. PPVautoCNAP was ?1.02±2.03% and PPVautoCNAP vs. PPVmanIBP was ?2.10±3.14%, suggesting that the automated CNAP® PPV-algorithm works well on both blood pressure waveforms but needs further clinical evaluation. 相似文献
1000.
Thomas H. Grandy Markus Werkle‐Bergner Christian Chicherio Florian Schmiedek Martin Lövdén Ulman Lindenberger 《Psychophysiology》2013,50(6):570-582
The individual alpha frequency (IAF) of the human EEG reflects systemic properties of the brain, is highly heritable, and relates to cognitive functioning. Not much is known about the modifiability of IAF by cognitive interventions. We report analyses of resting EEG from a large‐scale training study in which healthy younger (20–31 years, N = 30) and older (65–80 years, N = 28) adults practiced 12 cognitive tasks for ~100 1‐h sessions. EEG was recorded before and after the cognitive training intervention. In both age groups, IAF (and, in a control analysis, alpha amplitude) did not change, despite large gains in cognitive performance. As within‐session reliability and test‐retest stability were high for both age groups, imprecise measurements cannot account for the findings. In sum, IAF is highly stable in healthy adults up to 80 years, not easily modifiable by cognitive interventions alone, and thus qualifies as a stable neurophysiological trait marker. 相似文献