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41.
Ehling D Kennerknecht I Junge A Prager B Exeler R Behre B Horst J Schmitt-John T Bartsch O Wirth J 《American journal of medical genetics. Part A》2004,131(3):265-272
We describe two unrelated patients with cytogenetically visible deletions of 21q22.2-q22.3 and mild phenotypes. Both patients presented minor dysmorphic features including thin marfanoid build, facial asymmetry, downward-slanting palpebral fissures, depressed nasal bridge, small nose with bulbous tip, and mild mental retardation (MR). FISH and molecular studies indicated common deleted areas but different breakpoints. In patient 1, the breakpoint was fine mapped to a 5.2 kb interval between exon 5 and exon 8 of the ETS2 gene. The subtelomeric FISH probe was absent on one homologue 21 indicating a terminal deletion spanning approximately 7.9 Mb in size. In patient 2, the proximal breakpoint was determined to be 300-700 kb distal to ETS2, and the distal breakpoint 2.5-0.3 Mb from the 21q telomere, indicating an interstitial deletion sized approximately 4.7-7.3 Mb. The 21q- syndrome is rare and typically associated with a severe phenotype, but different outcomes depending on the size and location of the deleted area have been reported. Our data show that monosomy 21q of the area distal to the ETS2 gene, representing the terminal 7.9 Mb of 21q, may result in mild phenotypes comprising facial anomalies, thin marfanoid build, and mild MR, with or without signs of holoprosencephaly. 相似文献
42.
Hubert Sch?fer Katrin Klippert Petra Meuer Bettina Borsdorf Albrecht F Kiderlen Reinhard Burger 《Journal of interferon & cytokine research》2007,27(4):305-315
Interferon-gamma (IFN-gamma) plays a key role in the induction and maintenance of immunity against intracellular infectious agents. Compared to other species, little is known about the biology of this cytokine in the guinea pig (Cavia porcellus). We found that in contrast to humans and mice, IFN-gamma in the guinea pig did not induce the antiviral state, which in other species leads to protection of IFN-gamma -stimulated fibroblasts from the cytopathic effect (CPE) of subsequent viral infections. As an alternative strategy to detect and quantify guinea pig IFN-gamma activity in vitro, a reporter system using guinea pig fibroblasts transfected with a luciferase gene, which is regulated by an IFN-stimulated response element (ISRE), was established. With the help of the highly sensitive reporter assay system, the biologic activity of recombinant guinea pig IFN-gamma (GpIFN-gamma, from prokaryotic and eukaryotic expression systems was detected. The response to both native and recombinant GpIFN-gamma was inhibited by a rabbit antiserum directed against the recombinant cytokine expressed in Escherichia coli, demonstrating structural and functional homology of native and recombinant GpIFN-gamma. Stimulation with GpIFN-gamma, obtained from transfected cells, induced upregulation of MHC class I expression in a guinea pig fibroblast line. The restricted activity of GpIFN-gamma might have implications for this species' ability to control infections with intracellular pathogens. 相似文献
43.
Patrick S Fitch Vanessa Brown Bettina C Schock Madeleine Ennis Michael D Shields 《Annals of allergy, asthma & immunology》2003,90(4):429-433
BACKGROUND: In asthma there is increased expression of the Th2-type cytokine interleukin-4 (IL-4). IL-4 is important in immunoglobulin isotype switching to immunoglobulin E and adhesion of eosinophils to endothelium. OBJECTIVE: We hypothesized that levels of IL-4 in bronchoalveolar lavage (BAL) fluid would be increased in stable, atopic asthmatic children compared with controls and that levels of its physiologic inhibitor IL-4 soluble receptor alpha (IL-4sR alpha) would be correspondingly decreased. METHODS: One hundred sixteen children attending a children's hospital for elective surgery were recruited. A nonbronchoscopic BAL was performed, and IL-4 and IL-4sR alpha were measured in the BAL supernatants. RESULTS: There was no significant difference in IL-4 concentrations between atopic asthmatic children, atopic normal controls, and nonatopic normal controls [0.13 pg/mL (0.13 to 0.87) vs 0.13 pg/mL (0.13 to 0.41) vs 0.13 pg/mL (0.13 to 0.5), P = 0.65]. IL-4sR alpha levels were significantly increased in asthmatic patients compared with atopic controls [6.4 pg/mL (5.0 to 25.5) vs 5.0 pg/mL (5.0 to 9.9), P = 0.018], but not when compared with the nonatopic controls [5.2 pg/mL (5.0 to 10.6), P = 0.19]. CONCLUSIONS: Contrary to expectation, IL-4sR alpha levels are increased in BAL from stable asthmatic children compared with nonatopic controls, and we speculate that IL-4sR alpha is released by inflammatory cells in the airways to limit the proinflammatory effects of IL-4. 相似文献
44.
Eric Schulze‐Bahr Lars Eckardt Günter Breithardt Karlheinz Seidl Thomas Wichter Christian Wolpert Martin Borggrefe Wilhelm Haverkamp 《Human mutation》2005,26(1):61-61
In supplementation of previously published cardiac sodium channel (SCN5A) gene mutations that were cited in the text, in Table 2 and in Figure 2 we here apply an updated gene mutation nomenclature (Human Genome Variation Society, 2005) to facilitate mutation annotation comparison (SCN5A cDNA reference: NM_198056.1 or GI: 37622906; amino acid reference sequence: SWISS‐PROT entry Q14524, long splice variant, 2,016 amino acids): Mutation: c.2602delC Amino acid change: p.Glu868X Mutation: c.2581_2582delTT Amino acid change: p.Phe861Trp fsX90 Mutation: c.4477_4479delAAG Amino acid change: p.Lys1493del Mutation: c.5425C>A Amino acid change: p.Ser1812X 相似文献
45.
Few studies have examined the associations between environmental conditions and developing infant emotionality or the differential susceptibility to those conditions. The present longitudinal study aims to make a contribution to close that gap. We analyzed whether positive emotionality, negative emotionality/irritability, and withdrawal/fear at the end of the first year of life are predictable from preceding caregiver's depression/anxiety, social support, and sensitivity in the interaction with the infant while controlling for antecedent states of emotionality. Furthermore, the question of whether associations between maternal characteristics and subsequent fear are stronger in the subgroup of infants high in irritability as opposed to those who are low in irritability was investigated. Subjects were 101 healthy firstborn infants and their primary caregivers. Assessments were conducted at infant ages of 4, 8, and 12 months. Depression, anxiety, and the social support of the caregiver were assessed by questionnaire. Sensitivity in the caregiver-infant interaction was assessed by behavior observations within the scope of home visits. Temperament characteristics were observed in standardized laboratory episodes. Whereas negative emotionality and withdrawal/fear were significantly predictable from the maternal characteristics, no predictability could be shown for developing positive emotionality. There were indications of a stronger association between the maternal characteristics and developing withdrawal/fear in irritable infants. 相似文献
46.
Airway hyper-reactivity mediated by B-1 cell immunoglobulin M antibody generating complement C5a at 1 day post-immunization in a murine hapten model of non-atopic asthma
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Kawikova I Paliwal V Szczepanik M Itakura A Fukui M Campos RA Geba GP Homer RJ Iliopoulou BP Pober JS Tsuji RF Askenase PW 《Immunology》2004,113(2):234-245
Contact skin immunization of mice with reactive hapten antigen and subsequent airway challenge with the same hapten induces immediate airflow obstruction and subsequent airway hyper‐reactivity (AHR) to methacholine challenge, which is dependent on B cells but not on T cells. This responsiveness to airway challenge with antigen is elicited as early as 1 day postimmunization and can be adoptively transferred to naïve recipients via 1‐day immune cells. Responses are absent in 1‐day immune B‐cell‐deficient JH?/? mice and B‐1 B‐cell‐deficient xid male mice, as well as in recipients of 1‐day immune cells depleted of cells with the B‐1 cell phenotype (CD19+ B220+ CD5+). As B‐1 cells produce immunoglobulin M (IgM), we sought and found significantly increased numbers of anti‐hapten IgM‐producing cells in the spleen and lymph nodes of 1‐day immune wild‐type mice, but not in xid mice. Then, we passively immunized naive mice with anti‐hapten IgM monoclonal antibody and, following airway hapten challenge of the recipients, we showed both immediate airflow obstruction and AHR. In addition, AHR was absent in complement C5 and C5a receptor‐deficient mice. In summary, this study of the very early elicited phase of a hapten asthma model suggests, for the first time, a role of B‐1 cells in producing IgM to activate complement to rapidly mediate asthma airway reactivity only 1 day after immunization. 相似文献
47.
Serosal mesothelium retains vasculogenic potential. 总被引:1,自引:0,他引:1
Mesothelia comprise the epithelial covering of coelomic organs and line the cavities in which they are housed. Mesothelia contribute to the vasculature of the heart and the intestinal tract by developmental processes of epithelial-mesenchymal transition (EMT), migration, and differentiation into endothelial cells, vascular smooth muscle cells, and pericytes. Here, we establish a novel in vitro system to analyze the differentiative potential of mesothelia. Using explants from serosal mesothelium (the mesothelial covering of the gut), we demonstrate that much of the developmental program observed in embryonic mesothelia is retained in the adult structure. Namely, processes of epithelial spreading, EMT, and differentiation into smooth muscle cells from these cells are observed. Interestingly, we were unable to stimulate endothelial cell differentiation using serum or various signaling factors. Taken together, these data reveal that differentiated serosal cells retain vasculogenic potential and provide a generalizable model for future studies on the developmental and differentiative capacity of the mesothelial cell type. 相似文献
48.
Ines Santisteban Francisco X. Arredondo-Vega Susan Kelly Marianne Debre Alain Fischer Jean Louis Prignon Bettina Hilman Jane Eldahr David H. Dreyfus Erwin W. Gelfand P. Lynne Howell Michael S. Hershfield 《Human mutation》1995,5(3):243-250
Three new missense mutations (H15D, A83D, and A179D) and a new splicing defect (573 + 1G→A) in the 5′ splice site of intron 5 were among six mutant adenosine deaminase (ADA) alleles found in three unrelated patients with severe combined immunodeficiency disease, the most common phenotype associated with ADA deficiency. When expressed in vitro, the H15D, A83D, and A179D proteins lacked detectable ADA activity. The splicing defect caused skipping of exon 5, resulting in premature termination of translation and a reduced level of mRNA. H15D is the first naturally occurring mutation of a residue that coordinates directly with the enzyme-associated zinc ion. Molecular modeling based on the atomic coordinates of murine ADA suggests that the D15 mutation would create a cavity or gap between the zinc ion and the side chain carboxylate of D15. This could alter the ability of zinc to activate a water molecule postulated to play a role in the catalytic mechanism. A83 and A179 are not directly involved in the active site, but are conserved residues located respectively in a helix 4 and β strand 4 of the α/β barrel. Replacement of these small hydrophobic Ala residues with the charged, more bulky Asp side chain may distort ADA structure and affect enzyme stability or folding.© 1995 wiley-Liss, Inc. 相似文献
49.
50.
Wahrmann M Exner M Haidbauer B Schillinger M Regele H Körmöczi G Böhmig GA 《Human immunology》2005,66(5):526-534
On waiting lists, transplant candidates are routinely screened for potentially harmful complement-fixing alloantibodies using complement-dependent cytotoxicity (CDC) panel-reactive antibody (PRA) testing. We have recently developed a novel cell-independent assay for assessment of complement-activating panel reactivity ([C4d]FlowPRA), which is based on selective flow-cytometric detection of alloantibody-triggered C4 complement split product deposition to human leukocyte antigen (HLA)-coated FlowPRA beads. Serum specimens selected from 120 transplant candidates were evaluated by [C4d]FlowPRA (HLA class I vs II) in comparison with FlowPRA IgG alloantibody screening (HLA class I vs II), a method detecting both complement- and noncomplement-activating alloantibodies, and with CDC-PRA on separated T (T-CDC) or B cells (B-CDC, evaluation on platelet-absorbed sera). For each assay, >/=10% PRA reactivity was considered positive. Comparing complement-dependent PRA assays with standard FlowPRA, the specificity calculated for [C4d]FlowPRA (HLA class I: 92%; class II: 100%) was found to be superior to that of CDC testing (T-CDC-PRA: 79%; B-CDC-PRA: 86%). Because noncomplement-activating alloreactivities were not detected for both techniques, low sensitivities were calculated ([C4d]FlowPRA HLA class I: 61%; class II: 31%; T-CDC-PRA: 70%; B-CDC-PRA: 55%). Compared with CDC-PRA, [C4d]FlowPRA gave a high specificity (HLA class I compared with T-CDC: 89%, HLA class II compared with B-CDC: 95%) but, at least in part because of false-positive CDC results, a modest sensitivity (66% and 38%, respectively). For both HLA classes, we found a highly significant association between absolute [C4d]FlowPRA and CDC-PRA levels (p < 0.0001). Our results suggest that detection of C4 split product deposition to FlowPRA beads may represent an attractive HLA-specific and time-effective alternative to CDC-PRA screening. 相似文献