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排序方式: 共有1547条查询结果,搜索用时 17 毫秒
31.
Hengameh Abdollahpour Malik Alawi Fanny Kortüm Michael Beckstette Eva Seemanova Vladimír Komárek Georg Rosenberger Kerstin Kutsche 《European journal of human genetics : EJHG》2015,23(2):256-259
The recently proposed adaptor protein 4 (AP-4) deficiency syndrome comprises a group of congenital neurological disorders characterized by severe intellectual disability (ID), delayed or absent speech, hereditary spastic paraplegia, and growth retardation. AP-4 is a heterotetrameric protein complex with important functions in vesicle trafficking. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been reported in patients with the AP-4 deficiency phenotype. We describe two siblings from a non-consanguineous couple who presented with severe ID, absent speech, microcephaly, growth retardation, and progressive spastic tetraplegia. Whole-exome sequencing in the two patients identified the novel homozygous 2-bp deletion c.1160_1161delCA (p.(Thr387Argfs*30)) in AP4B1. Sanger sequencing confirmed the mutation in the siblings and revealed it in the heterozygous state in both parents. The AP4B1-associated phenotype has previously been assigned to spastic paraplegia-47. Identification of a novel AP4B1 alteration in two patients with clinical manifestations highly similar to other individuals with mutations affecting one of the four AP-4 subunits further supports the observation that loss of AP-4 assembly or functionality underlies the common clinical features in these patients and underscores the existence of the clinically recognizable AP-4 deficiency syndrome. 相似文献
32.
Nassim Hammoudi Marion Dhooge Romain Coriat Sarah Leblanc Maximilien Barret Benoit Bordacahar Frederic Beuvon Frederic Prat Fanny Maksimovic Stanislas Chaussade 《Digestive and liver disease》2019,51(2):299-303
Background and aims
Lynch syndrome (LS) is associated with an increased risk of small bowel tumors but routine screening is not recommended in international guidelines. The aim of our study was to determinate the prevalence of duodenal tumors in a French cohort of LS patients.Methods
Patients carrying a germline pathogenic variant in a MMR gene, supported by our local network, in which at least one upper endoscopy had been performed, were included. We registered the occurrence of duodenal lesions in those patients.Results
154 LS patients were identified including respectively 85 MSH2 and 41 MLH1 mutated patients respectively. Seven out of 154 (4.5%) had at least one duodenal lesion. Median age at diagnosis was 58 years (range: 49–73). The twelve lesions locations were: descending duodenum (n?=?7), genu inferius (n?=?2), duodenal bulb (n?=?1), ampulla (n?=?1), fourth duodenum (n?=?1). Three lesions were invasive adenocarcinomas. The incidence rate of duodenal lesions in patients with MSH2 or MLH1 pathogenic variants was respectively 7.1% (6 out of 85) and 2.4% (1 out of 41) emphasizing a trend toward increased risk of developing duodenal lesion in MSH2 mutated patients: OR: 5.17, IC95% (0.8–60.07), p?=?0.1307.Conclusion
Regarding this high prevalence rate, especially in MSH2 patients, regular duodenal screening during upper endoscopy should be considered in routine in LS patients. 相似文献33.
Mutations of the Imprinted CDKN1C Gene as a Cause of the Overgrowth Beckwith–Wiedemann Syndrome: Clinical Spectrum and Functional Characterization 下载免费PDF全文
Frederic Brioude Irène Netchine Francoise Praz Marilyne Le Jule Claire Calmel Didier Lacombe Patrick Edery Martin Catala Sylvie Odent Bertrand Isidor Stanislas Lyonnet Sabine Sigaudy Bruno Leheup Séverine Audebert‐Bellanger Lydie Burglen Fabienne Giuliano Jean‐Luc Alessandri Valérie Cormier‐Daire Fanny Laffargue Sophie Blesson Isabelle Coupier James Lespinasse Patricia Blanchet Odile Boute Clarisse Baumann Michel Polak Berenice Doray Alain Verloes Géraldine Viot Yves Le Bouc Sylvie Rossignol 《Human mutation》2015,36(9):894-902
Beckwith–Wiedemann syndrome (BWS) is an imprinting disorder associating macroglossia, abdominal wall defects, visceromegaly, and a high risk of childhood tumor. Molecular anomalies are mostly epigenetic; however, mutations of CDKN1C are implicated in 8% of cases, including both sporadic and familial forms. We aimed to describe the phenotype of BWS patients with CDKN1C mutations and develop a functional test for CDKN1C mutations. For each propositus, we sequenced the three exons and intron–exon boundaries of CDKN1C in patients presenting a BWS phenotype, including abdominal wall defects, without 11p15 methylation defects. We developed a functional test based on flow cytometry. We identified 37 mutations in 38 pedigrees (50 patients and seven fetuses). Analysis of parental samples when available showed that all mutations tested but one was inherited from the mother. The four missense mutations led to a less severe phenotype (lower frequency of exomphalos) than the other 33 mutations. The following four tumors occurred: one neuroblastoma, one ganglioneuroblastoma, one melanoma, and one acute lymphoid leukemia. Cases of BWS caused by CDKN1C mutations are not rare. CDKN1C sequencing should be performed for BWS patients presenting with abdominal wall defects or cleft palate without 11p15 methylation defects or body asymmetry, or in familial cases of BWS. 相似文献
34.
Gomez NN Fernandez MR Zirulnik F Gil E Scardapane L Ojeda MS Gimenez MS 《Experimental lung research》2003,29(7):485-502
Few studies are available about the role of dietary zinc (Zn) in respiratory diseases. Adult male rats were divided into 2 groups and fed respectively a moderate Zn-deficient diet and a Zn-adequate control diet. In lung tissue at 2 months, thiobarbituric acid-reactive species (TBARS), total glutathione, glutathione disulfide, protein carbonyls, metallothionein, and the activities of glutathione peroxidase (GPx), catalase, CuZn-superoxide dismutase (CuZnSOD) and glucose-6-phosphate dehydrogenase (G-6-PDH) were increased, but protein thiols decreased. In lung tissue at 4 months, TBARS, metallothionein, and the activities of CuZnSOD, Mn-superoxide dismutase (MnSOD) increased. The activities GPx, catalase, G-6-PDH were lower than control group. The changes were accompanied by histological alterations in Zn-deficient lung. The results provide evidence of the pro-oxidative effects of Zn-deficiency in lung, and suggest that the time of treatment play a key role in determining lung susceptibility to oxidative stress. 相似文献
35.
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
36.
37.
Harry Sokol Sophie Georgin-Lavialle Danielle Canioni Stéphane Barete Gandhi Damaj Erinn Soucie Julie Bruneau Marie-Olivia Chandesris Felipe Suarez Jean-Marie Launay Achille Aouba Catherine Grandpeix-Guyodo Fanny Lanternier Bernard Grosbois Christian de Gennes Pascal Cathébras Olivier Fain Nadia Hoyeau-Idrissi Patrice Dubreuil Olivier Lortholary Laurent Beaugerie Brigitte Ranque Olivier Hermine 《The Journal of allergy and clinical immunology》2013
38.
Yohan Nguyen Fanny Renois Nicolas Leveque Delphine Giusti Marcus Picard-Maureau Patrick Bruneval Paul Fornes Laurent Andreoletti 《Journal of clinical microbiology》2013,51(7):2288-2294
Viral detection in heart tissues has become a central issue for the diagnosis and exploration of the pathogenesis of idiopathic dilated cardiomyopathy (IDCM). In the present study, common cardiotropic viruses in 67 explanted heart samples of 31 IDCM adult patients were detected and semiquantified by using for the first time a new technology based on PCR assay coupled to electrospray ionization-time of flight mass spectrometry analysis (PCR-MS), with comparison to reference quantitative real-time PCR (RT-qPCR) assay. PCR-MS identified single or mixed enterovirus (EV) and parvovirus B19 (PVB19) infections in 27 (40.2%) of 67 samples, corresponding to 15 (48.3%) of the 31 patients, whereas RT-qPCR identified viral infections in 26 (38.8%) samples, corresponding to 16 (51.6%) of the patients. The PCR-MS results correlated well with EV and PVB19 detection by RT-qPCR (kappa = 0.85 [95% confidence interval {CI}, 0.72 to 1.00] and kappa = 0.82 [95% CI, 0.66 to 0.99], respectively). The levels of EV RNA (median, 550 [range, 178 to 3,200] copies/μg of total extracted nucleic acids) and of PVB19 DNA (median, 486 [range, 80 to 1,157] copies/μg of total extracted nucleic acids) were measured using PCR-MS and correlated with those obtained by RT-qPCR (r2 = 0.57, P = 0.002 and r2 = 0.64, P < 0.001 for EV and PVB19, respectively). No viruses other than EV and PVB19 strains were detected using the new PCR-MS technology, which is capable of simultaneously identifying 84 known human viruses in one assay. In conclusion, we identified single or mixed EV and PVB19 cardiac infections as potential causes of IDCM. The PCR-MS analysis appeared to be a valuable tool to rapidly detect and semiquantify common viruses in cardiac tissues and may be of major interest to better understand the role of viruses in unexplained cardiomyopathies. 相似文献
39.
Jeanne‐Marie Perotin Sandra Dury Fanny Renois Gaëtan Deslee Aurore Wolak Véronique Duval Christophe De Champs François Lebargy Laurent Andreoletti 《Journal of medical virology》2013,85(5):866-873
Few studies have evaluated the contribution of multiple virus and bacterial infections in acute exacerbation of chronic obstructive pulmonary disease. This study estimated the burden of multiple viral and bacterial respiratory infections in moderate to very severe chronic obstructive pulmonary disease patients that were prospectively followed‐up during a 12‐month pilot study. Clinical data were collected monthly and sputum was collected at the time of each acute exacerbation event. Classical culture techniques for bacteria and multiplex polymerase chain reaction (PCR) and microarray detection assays were performed to identify viral and atypical bacterial pathogens in the sputum. Overall, 51 patients were included and 45 acute exacerbation events were investigated clinically and microbiologically. Among the 45 acute exacerbation events, 44% had evidence of viral infection involving human rhinovirus (HRV) and metapneumovirus (hMPV) in 20% and 18%, respectively. Intracellular bacteria were not found in sputum by PCR. Common bacterial pathogens were identified in 42% of acute exacerbation patients, most frequently Branhamella catarrhalis, Streptococcus pneumoniae and Haemophilus influenzae. Viral or virus and bacteria co‐infections were detected in 27% of acute exacerbation events (n = 12) with HRV and hMPV involved in 92% of cases. Patients with co‐infections did not present greater clinical severity scores at exacerbation and more recurrence of acute exacerbation events at 3 and 6 months than those with single infections (P > 0.4). These results suggest that HRV and hMPV may be contributors or cofactors of AECOPD. These findings indicate that viral or virus and bacterial co‐infections do not impact significantly on the clinical severity of acute exacerbation of chronic obstructive pulmonary disease and recurrence at 3 and 6 months. J. Med. Virol. 85:866–873, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
40.
Rachmilewitz D Karmeli F Takabayashi K Hayashi T Leider-Trejo L Lee J Leoni LM Raz E 《Gastroenterology》2002,122(5):1428-1441
BACKGROUND & AIMS: Impaired mucosal barrier, cytokine imbalance, and dysregulated CD4(+) T cells play important roles in the pathogenesis of experimental colitis and human inflammatory bowel disease. Immunostimulatory DNA sequences (ISS-DNA) and their synthetic oligonucleotide analogs (ISS-ODNs) are derived from bacterial DNA, are potent activators of innate immunity at systemic and mucosal sites, and can rescue cells from death inflicted by different agents. We hypothesized that these combined effects of ISS-DNA could inhibit the damage to the colonic mucosa in chemically induced colitis and thereby limit subsequent intestinal inflammation. METHODS: The protective and the anti-inflammatory effect of ISS-ODN administration were assessed in dextran sodium sulfate-induced colitis and in 2 models of hapten-induced colitis in Balb/c mice. Similarly, these effects of ISS-ODN were assessed in spontaneous colitis occurring in IL-10 knockout mice. RESULTS: In all models of experimental and spontaneous colitis examined, ISS-ODN administration ameliorated clinical, biochemical, and histologic scores of colonic inflammation. ISS-ODN administration inhibited the induction of colonic proinflammatory cytokines and chemokines and suppressed the induction of colonic matrix metalloproteinases in both dextran sodium sulfate- and hapten-induced colitis. CONCLUSIONS: As the colon is continuously exposed to bacterial DNA, these findings suggest a physiologic, anti-inflammatory role for immunostimulatory DNA in the GI tract. Immunostimulatory DNA deserves further evaluation for the treatment of human inflammatory bowel disease. 相似文献