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991.
Background: Besides body mass index (BMI), new parameters have been developed to classify individual body shape.Aim: To investigate the relationship between BMI, waist circumference (WC), a body shape index (ABSI) and ABSI-adolescents among adolescents and verify which would better predict lower adiponectin/leptin (A/L) ratio and disturbances on glucose metabolism.Subjects and methods: A cross-sectional study with 197 Brazilian adolescents of 14–18?years. Serum leptin, adiponectin, glucose and insulin were measured. A/L ratio, ABSI, ABSI-adolescents, BMI, homeostasis model assessment estimates of insulin resistance (HOMA-IR) and β-cell function (HOMA-β) and the quantitative insulin sensitivity check index (QUICKI) were calculated.Results: ABSI-adolescents positively correlated with WC (r?=?0.83, p?0.0001) and BMI (r?=?0.66, p?0.0001), but stronger correlations were observed between WC and BMI (r?=?0.95, p?0.0001). ABSI-adolescents, BMI and WC negatively correlated with A/L ratio (all p?0.0001). The correlation between BMI and A/L ratio was the strongest (r?=??0.63, p?0.001). A/L ratio, BMI, WC and ABSI-adolescents correlated with markers of glucose metabolism (all p?0.0001) and the strongest correlation was observed with BMI (QUICKI: r?=??0.75; HOMA-IR: r?=?0.76; HOMA-β: r?=?0.77; insulin: r?=?0.79). Associations were confirmed by linear regression analysis, adjusted for sex and age.Conclusions: ABSI-adolescents, but not ABSI, was related to A/L ratio and to markers of glucose metabolism, but not more strongly than BMI and WC. 相似文献
992.
Vernon J. Lee Jonathan Yap Sebastian Maurer-Stroh Raphael T.C. Lee Frank Eisenhaber Joshua K. Tay Pei Jun Ting Jin Phang Loh Christopher W. Wong Boon Huan Tan Evelyn S.C. Koay Paul M. Kelly Martin L. Hibberd 《Journal of clinical virology》2011,50(2):104-108
BackgroundAntiviral post-exposure prophylaxis with oseltamivir has been used as a strategy in mitigating the Influenza A (H1N1-2009) pandemic. There have been few reports of well-documented prophylaxis failures and the reasons for failure.ObjectivesWe report herein a series of 10 cases of prophylaxis failures and explore the reasons behind their prophylaxis failure.Study designIn the early pandemic phase, the military employed oseltamivir post-exposure ring-prophylaxis of affected units. From June 22 to July 30, 2009, cases of laboratory-confirmed prophylaxis failures were identified. Nasopharyngeal swabs were collected and tested by PCR. Samples with sufficient RNA material were sent for whole genome sequencing, and screened for mutations that confer oseltamivir resistance, especially the H275Y mutation.ResultsTen cases of laboratory-confirmed prophylaxis failure were identified, with a mean age of 22.3 years. One case was asymptomatic; the remaining 9 had fever or cough but without severe complications. The mean duration of exposure before starting oseltamivir was 1.9 days (SD 0.9), while the mean duration of oseltamivir consumption before symptom onset was 1.9 days (SD 1.4). None of the samples had the H275Y mutation or other known mutations that confer resistance. From the whole genome sequencing, several mutations at the HA (T220S, E275V, T333A, D239G); PB2 (K660R, L607V, V292I); NS1 (F103S), and NP (W104G) gene segments were detected, but none of them were likely to result in anti-viral resistance.ConclusionsPrimary prophylaxis failures exhibited mild symptoms without complications; all did not have the H275Y mutation and were unlikely to result from other mutations. 相似文献
993.
Gastric polyps are not uncommonly encountered at endoscopy and their discovery will normally precipitate a biopsy to determine the nature of the lesion. The foundation for arriving at the correct diagnosis is to be aware of the entities that exist and to this end we offer a classification based on histogenesis to aid the diagnostic endeavour. The vast majority of polyps encountered are epithelial in origin and so this review will focus mainly on epithelial polyps. Like elsewhere in the gastrointestinal tract, epithelial polyps can be associated with dysplasia which can be challenging to diagnose and grade. Dysplasia in the upper gastrointestinal tract has undergone recent reclassification and so we provide update and discussion on this neoplastic process as it applies to the stomach. 相似文献
994.
Lin Z Hegarty JP Cappel JA Yu W Chen X Faber P Wang Y Kelly AA Poritz LS Peterson BZ Schreiber S Fan JB Koltun WA 《Clinical genetics》2011,80(1):59-67
Lin Z, Hegarty JP, Cappel JA, Yu W, Chen X, Faber P, Wang Y, Kelly AA, Poritz LS, Peterson BZ, Schreiber S, Fan J‐B, Koltun WA. Identification of disease‐associated DNA methylation in intestinal tissues from patients with inflammatory bowel disease. Overwhelming evidence supports the theory that inflammatory bowel disease (IBD) is caused by a complex interplay between genetic predispositions of multiple genes, combined with an abnormal interaction with environmental factors. It is becoming apparent that epigenetic factors can have a significant contribution in the pathogenesis of disease. Changes in the methylation state of IBD‐associated genes could significantly alter levels of gene expression, potentially contributing to disease onset and progression. We have explored the role of DNA methylation in IBD pathogenesis. DNA methylation profiles (1505 CpG sites of 807 genes) of matched diseased (n = 26) and non‐diseased (n = 26) intestinal tissues from 26 patients with IBD [Crohn's disease (CD) n = 9, ulcerative colitis (UC) n = 17] were profiled using the GoldenGate? methylation assay. After an initial identification of a panel of 50 differentially methylated CpG sites from a training set (14 non‐diseased and 14 diseased tissues) and subsequent validation with a testing set (12 non‐diseased and 12 diseased tissues), we identified seven CpG sites that are differentially methylated in intestinal tissues of IBD patients. We have also identified changes in DNA methylation associated with the two major IBD subtypes, CD and UC. This study reports IBD‐associated changes in DNA methylation in intestinal tissue, which may be disease subtype‐specific. 相似文献
995.
Allen IC Moore CB Schneider M Lei Y Davis BK Scull MA Gris D Roney KE Zimmermann AG Bowzard JB Ranjan P Monroe KM Pickles RJ Sambhara S Ting JP 《Immunity》2011,34(6):854-865
The nucleotide-binding domain and leucine-rich-repeat-containing (NLR) proteins regulate innate immunity. Although the positive regulatory impact of NLRs is clear, their inhibitory roles are not well defined. We showed that Nlrx1(-/-) mice exhibited increased expression of antiviral signaling molecules IFN-β, STAT2, OAS1, and IL-6 after influenza virus infection. Consistent with increased inflammation, Nlrx1(-/-) mice exhibited marked morbidity and histopathology. Infection of these mice with an influenza strain that carries a mutated NS-1 protein, which normally prevents IFN induction by interaction with?RNA and the intracellular RNA sensor RIG-I, further exacerbated IL-6 and type I IFN signaling. NLRX1 also weakened cytokine responses to the 2009 H1N1 pandemic influenza virus in human cells.?Mechanistically, Nlrx1 deletion led to constitutive interaction of MAVS and RIG-I. Additionally, an inhibitory function is identified for NLRX1 during LPS activation of macrophages where the MAVS-RIG-I pathway was not involved. NLRX1 interacts with TRAF6 and inhibits NF-κB activation. Thus, NLRX1 functions as a checkpoint of overzealous inflammation. 相似文献
996.
997.
Alhamadsheh MM Connelly S Cho A Reixach N Powers ET Pan DW Wilson IA Kelly JW Graef IA 《Science translational medicine》2011,3(97):97ra81
A valine-to-isoleucine mutation at position 122 of the serum protein transthyretin (TTR), found in 3 to 4% of African Americans, alters its stability, leading to amyloidogenesis and cardiomyopathy. In addition, 10 to 15% of individuals older than 65 years develop senile systemic amyloidosis and cardiac TTR deposits because of wild-type TTR amyloidogenesis. Although several drugs are in development, no approved therapies for TTR amyloid cardiomyopathy are yet available, so the identification of additional compounds that prevent amyloid-mediated cardiotoxicity is needed. To this aim, we developed a fluorescence polarization-based high-throughput screen and used it to identify several new chemical scaffolds that target TTR. These compounds were potent kinetic stabilizers of TTR and prevented TTR tetramer dissociation, partial unfolding, and aggregation of both wild type and the most common cardiomyopathy-associated TTR mutant, V122I-TTR. High-resolution co-crystal structures and characterization of the binding energetics revealed how these diverse structures bound to tetrameric TTR. These compounds effectively inhibited the proteotoxicity of V122I-TTR toward human cardiomyocytes. Several of these ligands stabilized TTR in human serum more effectively than diflunisal, which is a well-studied inhibitor of TTR aggregation, and may be promising leads for the treatment or prevention of TTR-mediated cardiomyopathy. 相似文献
998.
Huang Y Simms AE Mazur A Wang S León NR Jones B Aziz N Kelly T 《Clinical & experimental metastasis》2011,28(6):567-579
Fibroblast activation protein-α (FAP) is a cell surface, serine protease of the post-prolyl peptidase family that is expressed
in human breast cancer but not in normal tissues. Previously, we showed that FAP expression increased tumor growth rates in
a mouse model of human breast cancer. Here the role of the proteolytic activities of FAP in promoting tumor growth, matrix
degradation and invasion was investigated. Mammary fat pads of female SCID mice were inoculated with breast cancer cells that
express FAP and the mice treated with normal saline or Val-boroPro (talabostat); Glu-boroPro (PT-630); or 1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine (LAF-237) that inhibit prolyl peptidases. Other mice were injected with breast cancer cells expressing a catalytically
inactive mutant of FAP and did not receive inhibitor treatment. PT-630 and LAF-237 did not slow growth of tumors produced
by any of the three cell lines expressing FAP. Talabostat slightly decreased the growth rates of the FAP-expressing tumors
but because PT-630 and LAF-237 did not, the growth retardation was likely not related to the inhibition of FAP or the related
post-prolyl peptidase dipeptidyl peptidase IV. Breast cancer cells expressing a catalytically inactive mutant of FAP (FAPS624A) also produced tumors that grew rapidly. In vitro studies revealed that cells expressing wild type FAP or FAPS624A degrade extracellular matrix (ECM) more extensively, accumulate higher levels of matrix metalloproteinase-9 (MMP-9) in conditioned
medium, are more invasive in type I collagen gels, and have altered signaling compared to control transfectants that do not
express FAP and form slow growing tumors. We conclude that the proteolytic activity of FAP participates in matrix degradation,
but other functions of the protein stimulate increased tumor growth. 相似文献
999.
Griffin ÉW Mullally S Foley C Warmington SA O'Mara SM Kelly AM 《Physiology & behavior》2011,104(5):934-941
Physical activity has been reported to improve cognitive function in humans and rodents, possibly via a brain-derived neurotrophic factor (BDNF)-regulated mechanism. In this study of human subjects, we have assessed the effects of acute and chronic exercise on performance of a face-name matching task, which recruits the hippocampus and associated structures of the medial temporal lobe, and the Stroop word-colour task, which does not, and have assessed circulating concentrations of BDNF and IGF-1 in parallel. The results show that a short period of high-intensity cycling results in enhancements in performance of the face-name matching, but not the Stroop, task. These changes in cognitive function were paralleled by increased concentration of BDNF, but not IGF-1, in the serum of exercising subjects. 3 weeks of cycling training had no effect on cardiovascular fitness, as assessed by VO2 scores, cognitive function, or serum BDNF concentration. Increases in fitness, cognitive function and serum BDNF response to acute exercise were observed following 5 weeks of aerobic training. These data indicate that both acute and chronic exercise improve medial temporal lobe function concomitant with increased concentrations of BDNF in the serum, suggesting a possible functional role for this neurotrophic factor in exercise-induced cognitive enhancement in humans. 相似文献
1000.
Wang RY Covault KK Halcrow EM Gardner AJ Cao X Newcomb RL Dauben RD Chang AC 《Molecular genetics and metabolism》2011,104(4):592-596