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31.
Wollmer MA Papassotiropoulos A Streffer JR Grimaldi LM Kapaki E Salani G Paraskevas GP Maddalena A de Quervain D Bieber C Umbricht D Lemke U Bosshardt S Degonda N Henke K Hegi T Jung HH Pasch T Hock C Nitsch RM 《Psychiatric genetics》2002,12(3):155-160
Tissue inhibitor of metalloproteinases 1 (TIMP-1) inhibits several proteinases including a disintegrin and metalloproteinase 10 (ADAM10), a major alpha-secretase that cleaves the beta-amyloid precursor protein within its amyloidogenic Abeta domain. The gene encoding TIMP-1 (TIMP 1) maps to the short arm of the X chromosome, in a region previously suggested as conferring genetic susceptibility for Alzheimer's disease (AD). To determine whether genetic variability of TIMP 1 contributes to the pathogenesis of AD, we analysed one single nucleotide polymorphism within TIMP 1 and one single nucleotide polymorphism in the 5'-untranslated region of TIMP 1 in patients with AD and control subjects from two independent and ethnically different populations. We did not observe any association between TIMP 1 genotypes and the diagnosis of AD in men or women. We also measured TIMP-1 protein levels in the cerebrospinal fluid of patients with AD, healthy control subjects, and patients with other neurological disorders. TIMP-1 levels were similar in all groups. In addition, no significant differences were observed after stratification for TIMP 1 genotypes. Our data show that neither genetic variability nor protein levels of TIMP-1 are associated with AD. 相似文献
32.
Extrinsic risk factors for compromised blood flow in the vertebral artery: anatomical observations of the transverse foramina from C3 to C7 总被引:2,自引:0,他引:2
Cagnie B Barbaix E Vinck E D'Herde K Cambier D 《Surgical and radiologic anatomy : SRA》2005,27(4):312-316
The vertebral artery (VA) is often involved in the occurrence of complications after spinal manipulative therapy. Due to osteophytes
compressing the VA anteriorly from the uncinate process or posteriorly from the facet complex, the VAs are susceptible to
trauma in the transverse foramina. Such altered anatomical configurations are of major clinical significance, as spinal manipulations
may result in dissection of the VA with serious consequences for the blood supply to the vertebrobasilar region. The purpose
of this study is to describe numerous structural features of the third to seventh cervical vertebrae in order to contribute
to the understanding of pathological conditions related to the VA. The minimal and maximal diameter of 111 transverse foramina
in dry cervical vertebrae were studied. The presence of osteophytes and their influence on the VA were evaluated at the vertebral
body and at the superior and inferior articular facets. The diameter of the transverse foramina increased from C3 to C6, while
the transverse foramina of C7 had the smallest diameter. At all levels the mean dimensions of the left foramina were greater
than those of the right side. Osteophytes from the uncinate process of C5 and C6 vertebrae were found in over 60% of dry vertebrae.
Osteophytes from the zygapophyseal joints were more frequent at C3 and C4 vertebrae. About half of the osteophytes of the
uncinate and of the superior articular process partially covered the transverse foramina. This was less common with those
of the inferior articular facets. Osteophytes covering the transverse foramen force the VAs to meander around these obstructions,
causing narrowing through external compression and are potential sites of trauma to the VAs potentially even leading to dissection.
We strongly advocate that screening protocols for vertebrobasilar insufficiency (VBI) be used prior to any manipulation of
the cervical spine and should include not only extension and rotation but any starting position from which the planned manipulation
will be performed. 相似文献
33.
Johann Kaspar Lieberwirth Pascal Joset Anja Heinze Julia Hentschel Anja Stein Antonella Iannaccone Katharina Steindl Alma Kuechler Rami Abou Jamra 《European journal of human genetics : EJHG》2021,29(5):808
Perinatal mortality is a heavy burden for both affected parents and physicians. However, the underlying genetic causes have not been sufficiently investigated and most cases remain without diagnosis. This impedes appropriate counseling or therapy. We describe four affected children of two unrelated families with cardiomyopathy, hydrops fetalis, or cystic hygroma that all deceased perinatally. In the four patients, we found the following homozygous loss of function (LoF) variants in SLC30A5 NM_022902.4:c.832_836del p.(Ile278Phefs*33) and NM_022902.4:c.1981_1982del p.(His661Tyrfs*10). Knockout of SLC30A5 has previously been shown a cardiac phenotype in mouse models and no homozygous LoF variants in SLC30A5 are currently described in gnomAD. Taken together, we present SLC30A5 as a new gene for a severe and perinatally lethal form of cardiomyopathy.Subject terms: Cardiovascular diseases, Development, Medical genetics, Medical genomics 相似文献
34.
The methionine allele of the COMT polymorphism impairs prefrontal cognition in children and adolescents with ADHD 总被引:9,自引:0,他引:9
Bellgrove MA Domschke K Hawi Z Kirley A Mullins C Robertson IH Gill M 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2005,163(3):352-360
ADHD is a highly heritable psychiatric disorder of childhood. A functional polymorphism (Val158Met) of the catechol-O-methyltransferase (COMT) gene has attracted interest as a candidate gene for ADHD. The high-activity valine variant of this polymorphism degrades prefrontal dopamine three to four times more quickly than the low-activity methionine variant and could therefore contribute to the proposed hypodopaminergic state in ADHD. Here we tested for association of this polymorphism with ADHD and examined its influence on prefrontal cognition in ADHD. We have previously reported no association of the Val158Met COMT gene polymorphism in 94 Irish ADHD families (Hawi et al. (2000) Am J Med Genet 96:282–284). Here we re-examined this finding with an extended sample of 179 ADHD cases using a family control design. We also examined the performance of children and adolescents with ADHD (n=61) on a standardised test of sustained attention. Analysis confirmed the absence of an association between the Val158Met COMT gene polymorphism and the clinical phenotype of ADHD. COMT genotype, however, affected prefrontal cognition in ADHD: ADHD children who were homozygous for the valine variant had significantly better sustained attention than those ADHD children possessing at least one copy of the methionine variant. Children possessing the methionine variant performed significantly below age-related norms on tests of sustained attention. Contrary to expectations, the methionine variant of the Val158Met COMT gene polymorphism impaired prefrontally-mediated cognition in ADHD. This effect may be understood by positing a hyper-functioning of prefrontal dopaminergic systems. Against this background, the slower clearance of dopamine associated with the methionine variant of the COMT gene polymorphism may be disadvantageous to cognition in ADHD.Mark Bellgrove and Katharina Domschke contributed equally to this work and should therefore both be considered first authors. The work reported herein was supported by a grant from the Irish Health Research Board. 相似文献
35.
Differences in maintenance of CD8+ and CD4+ bacteria-specific effector-memory T cell populations 总被引:1,自引:0,他引:1
Schiemann M Busch V Linkemann K Huster KM Busch DH 《European journal of immunology》2003,33(10):2875-2885
Our knowledge about the kinetics and dynamics of complex pathogen-specific CD8(+) T cell responses and the in vivo development of CD8(+) memory T cells has increased substantially over the past years; in comparison, relatively little is known about the CD4(+) T cell compartment. We monitored and directly compared the phenotypical changes of pathogen (Listeria monocytogenes)-specific CD8(+) and CD4(+) T cell responses under conditions leading to effective and long-lasting protective immunity. We found that the general kinetics of bacteria-specific CD8(+) and CD4(+) T cells during the effector and post-effector phases are synchronized. However, later during the memory phase, CD8(+) and CD4(+) T cell populations differ substantially. Whereas CD8(+) memory T cell populations with immediate effector function are readily detectable in lymphoid and non-lymphoid tissues and remain remarkably stable in size, antigen-specific CD4(+) effector-memory T cells decline continuously in frequency over time. These findings have important implications for the better understanding of the in vivo development of protective immunity towards intracellular pathogens. 相似文献
36.
37.
Finn Jung Katharina Burger Raphaela Staltner Annette Brandt Sebastian Mueller Ina Bergheim 《Nutrients》2021,13(5)
Changes in intestinal microbiome and barrier function are critical in the development of alcohol-related liver disease (ALD). Here, we determined the effects of a one-week alcohol withdrawal on parameters of intestinal barrier function in heavy drinkers with ALD in comparison to healthy non-drinkers (controls). In serum samples of 17 controls (m = 10/f = 7) and 37 age-matched ALD patients (m = 26/f = 11) undergoing a one-week alcohol withdrawal, markers of liver health and intestinal barrier function were assessed. Liver damage, e.g., fibrosis and hepatic steatosis, were assessed using FibroScan. Before alcohol withdrawal, markers of liver damage, lipopolysaccharide binding protein (LBP) and overall TLR4/TLR2 ligands in serum were significantly higher in ALD patients than in controls, whereas intestinal fatty acid binding protein (I-FABP) and zonulin protein concentrations in serum were lower. All parameters, with the exception of LBP, were significantly improved after alcohol withdrawal; however, not to the level of controls. Our data suggest that one-week of abstinence improves markers of intestinal barrier function and liver health in ALD patients. 相似文献
38.
Katharina Voigt Emily Giddens Romana Stark Emma Frisch Neda Moskovsky Naomi Kakoschke Julie C. Stout Mark A. Bellgrove Zane B. Andrews Antonio Verdejo-Garcia 《Nutrients》2021,13(6)
Food homeostatic states (hunger and satiety) influence the cognitive systems regulating impulsive responses, but the direction and specific mechanisms involved in this effect remain elusive. We examined how fasting, and satiety, affect cognitive mechanisms underpinning disinhibition using a novel framework and a gamified test-battery. Thirty-four participants completed the test-battery measuring three cognitive facets of disinhibition: attentional control, information gathering and monitoring of feedback, across two experimental sessions: one after overnight fasting and another after a standardised meal. Homeostatic state was assessed using subjective self-reports and biological markers (i.e., blood-derived liver-expressed antimicrobial protein 2 (LEAP-2), insulin and leptin). We found that participants who experienced greater subjective hunger during the satiety session were more impulsive in the information gathering task; results were not confounded by changes in mood or anxiety. Homeostatic state did not significantly influence disinhibition mechanisms linked to attentional control or feedback monitoring. However, we found a significant interaction between homeostatic state and LEAP-2 on attentional control, with higher LEAP-2 associated with faster reaction times in the fasted condition only. Our findings indicate lingering hunger after eating increases impulsive behaviour via reduced information gathering. These findings identify a novel mechanism that may underpin the tendency to overeat and/or engage in broader impulsive behaviours. 相似文献
39.
40.
Carolin Lepa Sascha Hoppe Antje Stber Boris V. Skryabin Laura Katharina Sievers Barbara Heitplatz Giuliano Ciarimboli Ute Neugebauer Maja T. Lindenmeyer Clemens D. Cohen Hannes C.A. Drexler Peter Boor Thomas Weide Hermann Pavenstdt Britta George 《Journal of the American Society of Nephrology : JASN》2021,32(2):357
BackgroundInjury to kidney podocytes often results in chronic glomerular disease and consecutive nephron malfunction. For most glomerular diseases, targeted therapies are lacking. Thus, it is important to identify novel signaling pathways contributing to glomerular disease. Neurotrophic tyrosine kinase receptor 3 (TrkC) is expressed in podocytes and the protein transmits signals to the podocyte actin cytoskeleton.MethodsNephron-specific TrkC knockout (TrkC-KO) and nephron-specific TrkC-overexpressing (TrkC-OE) mice were generated to dissect the role of TrkC in nephron development and maintenance.ResultsBoth TrkC-KO and TrkC-OE mice exhibited enlarged glomeruli, mesangial proliferation, basement membrane thickening, albuminuria, podocyte loss, and aspects of FSGS during aging. Igf1 receptor (Igf1R)–associated gene expression was dysregulated in TrkC-KO mouse glomeruli. Phosphoproteins associated with insulin, erb-b2 receptor tyrosine kinase (Erbb), and Toll-like receptor signaling were enriched in lysates of podocytes treated with the TrkC ligand neurotrophin-3 (Nt-3). Activation of TrkC by Nt-3 resulted in phosphorylation of the Igf1R on activating tyrosine residues in podocytes. Igf1R phosphorylation was increased in TrkC-OE mouse kidneys while it was decreased in TrkC-KO kidneys. Furthermore, TrkC expression was elevated in glomerular tissue of patients with diabetic kidney disease compared with control glomerular tissue.ConclusionsOur results show that TrkC is essential for maintaining glomerular integrity. Furthermore, TrkC modulates Igf-related signaling in podocytes. 相似文献