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21.
A human-mouse chimera of the alpha3alpha4alpha5(IV) collagen protomer rescues the renal phenotype in Col4a3-/- Alport mice 下载免费PDF全文
Heidet L Borza DB Jouin M Sich M Mattei MG Sado Y Hudson BG Hastie N Antignac C Gubler MC 《The American journal of pathology》2003,163(4):1633-1644
Collagen IV is a major structural component of basement membranes. In the glomerular basement membrane (GBM) of the kidney, the alpha3, alpha4, and alpha5(IV) collagen chains form a distinct network that is essential for the long-term stability of the glomerular filtration barrier, and is absent in most patients affected with Alport syndrome, a progressive inherited nephropathy associated with mutation in COL4A3, COL4A4, or COL4A5 genes. To investigate, in vivo, the regulation of the expression, assembly, and function of the alpha3alpha4alpha5(IV) protomer, we have generated a yeast artificial chromosome transgenic line of mice carrying the human COL4A3-COL4A4 locus. Transgenic mice expressed the human alpha3 and alpha4(IV) chains in a tissue-specific manner. In the kidney, when expressed onto a Col4a3(-/-) background, the human alpha3(IV) chain restored the expression of and co-assembled with the mouse alpha4 and alpha5(IV) chains specifically at sites where the human alpha3(IV) was expressed, demonstrating that the expression of all three chains is required for network assembly. The co-assembly of the human and mouse chains into a hybrid network in the GBM restores a functional GBM and rescues the Alport phenotype, providing further evidence that defective assembly of the alpha3-alpha4-alpha5(IV) protomer, caused by mutations in any of the three chains, is the pathogenic mechanism responsible for the disease. This line of mice, humanized for the alpha3(IV) collagen chain, will also provide a valuable model for studying the pathogenesis of Goodpasture syndrome, an autoimmune disease caused by antibodies against this chain. 相似文献
22.
Tartour Eric; de la Salle Henri; de la Salle Corinne; Teillaud Christophe; Camoin Luc; Galinha Annie; Latour Sylvain; Hanau Daniel; Fridman Wolf H.; Sautes Catherine 《International immunology》1993,5(8):859-868
Low affinity FcR are a heterogeneous group of glycoproteinswhich exist in transmembrane (TM) as well as in soluble forms.Two membrane isoforms of the murine type II FcR, FcRilb1 andFc;Rilb2, have been described. They result from the translationof alternatively spliced premRNA, FcRilb2 lacking sequencesof the first intracytoplasmic domain (IC1). Soluble forms ofFcR (sFcR) have previously been shown to result from proteolysisof membrane receptors. We report here the identification, inmacrophages, of a mRNA derived from the FCRll gene by splicingexons encoding the TM and IC1 domains, i.e. corresponding toa TM-deleted FcRllb2 mRNA. A soluble protein possibly encodedby this mRNA was identified in macrophage supernatants. In accordancewith FcR nomenclature, we propose to name this new FcRll IsoformFcRllb3. It is the most abundant 8FcR present in serum, as comparedwith 8FcR resulting from cleavage of membrane FcR. 相似文献
23.
Souriau J Gimenes M Blouin C Benbrik I Benbrik E Churakowskyi A Churakowskyi B 《American journal of medical genetics. Part A》2005,135(3):278-281
Kabuki syndrome (KS) is associated with multiple organ system involvement. Characteristic features include long palpebral fissures with everted lower lids, prominent ears, skeletal abnormalities, mental retardation, and short stature. An increased incidence of infection has been reported in KS, and a few patients have been noted to have immune defects. However, the frequency and severity of the immune deficiency has not been clearly defined. Immunologic evaluation of 19 consecutive individuals with KS was performed at The Children's Hospital of Philadelphia. Decreased IgA levels were noted in 15/19 individuals (79%), 2 of whom had undetectable levels. Eight patients (42%) also had low total IgG levels. Specific IgG subclass abnormalities were found in 6 of 13 patients evaluated. IgM levels were less frequently decreased. One patient failed to generate anti-tetanus antibodies despite immunization. This study suggests that hypogammaglobulinemia is a frequent finding in children with KS. The pattern of antibody abnormalities seen in children with KS resembles common variable immune deficiency (CVID). Due to this increased susceptibility to infection, children with KS should have immunologic evaluations at the time of diagnosis in order to reduce preventable morbidity and mortality. 相似文献
24.
The dosimetric characteristics for a new brachytherapy seed source (I-Plant model 3600) were measured using LiF thermoluminescent dosimeters and appropriate phantom materials in conformance with the methodology and guidance provided by the AAPM Task Group 43. The I-Plant model 3600 is the successor to the I-Plant model 3500. The major difference between these sources is that the model 3600 contains a leaded-glass core to provide radio-opacity (while the model 3500 contains a silver core), which does not produce spectral contamination upon neutron activation. The dose rate constant lambda for the model 3600 was determined to be 1.00 Gy h(-1) U(-1) (with a 6% overall relative standard deviation), compared to 1.01 cGy h(-1) U(-1) reported for the model 3500 in previous studies. The remaining dosimetric characteristics also are similar for both sources. 相似文献
25.
Partha Biswas Govindsamy Kumaramanickavel Corinne Stoetzel Renaud Quillet Jyotirmay Biswas Elisabeth Lajeunie Dominique Renier Fabienne Perrin‐Schmitt 《American journal of medical genetics. Part A》2002,109(3):218-225
Saethre‐Chotzen syndrome is an autosomal dominant disease characterized by craniosynostosis, ptosis, and limb and external ear abnormalities. Variable expressivity is a well‐known phenomenon in this disorder. A large Indian family has been recently identified as carrying a nonsense TWIST mutation (Q28 X) in 17 members, of whom 16 were examined in detail. Only 4 (25%) of the patients showed patent craniostenosis, namely, oxycephaly. The penetrance of craniosynostosis in this family is lower than previously reported in the literature. Fifteen patients (93%) had moderate to severe ptosis. Minor limb and external ear abnormalities were present in most patients. Eyelid features were the hallmark of the disease for 12 members of the family, suggesting that mutations in TWIST may lead to a phenotype with mainly palpebral features and no craniostenosis. The clinical analysis of this large family clearly illustrates the significant variable expressivity, probably related to haploinsufficiency because of the TWIST mutation. This phenotypic variability remains unclear but could be the result of modifier genes and/or genetic background effect, as noticed previously in the transgenic twist‐null heterozygous mice. © 2002 Wiley‐Liss, Inc. 相似文献
26.
Joanne Young Barbara Leggett Corinne Gustafson Michael Ward Jeffrey Searle Lesley Thomas Ron Buttenshaw Georgia Chenevix-Trench 《Human mutation》1993,2(5):351-354
Genomic instability, as demonstrated by the presence of additional alleles at short tandemly repeated (STR) loci, has recently been observed in colorectal tumours from individuals with hereditary non-polyposis colorectal cancer (HNPCC), and in some sporadic tumours. These neoplasms have been called replication error positive (RER+). In this study, we confirm the presence of genomic instability in a proportion of unselected colorectal carcinomas but find no evidence of instability in adenomas. We further report replication errors in a tetranucleotide sequence, and in STRs within two tumour suppressor genes. 108 colorectal adenocarcinomas and 46 adenomas were analysed for the presence of variant bands at 4–15 microsatellite markers. Seven (6.5%) of carcinomas were RER+, four of which originated from the proximal colon. Analysis of the adenomas and of matched adenoma-carcinoma and carcinoma-metastatic samples from four patients suggests that the replication errors may occur during the development of carcinomas but are rare in adenomas. © 1993 Wiley-Liss, Inc. 相似文献
27.
Corinne Besnard-Gurin Webster Cavenee Irene Newshams 《Genes, chromosomes & cancer》1995,13(3):145-150
Translocations and deletions involving chromosomal band 22q 11 are common genetic aberrations in malignant rhabdoid tumors. Previous molecular analyses of a t(11; 22) in the malignant rhabdoid tumor cell line TM87-16 localized the breakpoint distal to BCR on 22q 11. In the present report, we have further refined the map position of this breakpoint between CRYBB2 and D22S258. Moreover, the D22S258, CRYBA4, D22S300, D22SI, and D22S310 loci, which lie between CRYBB2 and D22S42, were found to be deleted, presumably as a result of the translocation event. The identification of this deletion of at least 2 Mb on the long arm of chromosome 22 should be helpful for mapping the gene(s) in the region involved in the development of malignant rhabdoid tumors as well as providing insights into the mechanisms of chromosomal translocation in human solid tumors. 相似文献
28.
Hordijk José A. Verbruggen Sascha C. Buysse Corinne M. Utens Elisabeth M. Joosten Koen F. Dulfer Karolijn 《Quality of life research》2022,31(9):2615-2617
Quality of Life Research - 相似文献
29.
Mathilde Chataigner Marie Martin Cline Lucas Veronique Pallet Sophie Lay Alexis Mehaignerie Elodie Bouvret Anne-Laure Dinel Corinne Joffre 《Nutrients》2021,13(3)
Neuroinflammation constitutes a normal part of the brain immune response orchestrated by microglial cells. However, a sustained and uncontrolled production of proinflammatory factors together with microglial activation contribute to the onset of a chronic low-grade inflammation, leading to neuronal damage and cognitive as well as behavioral impairments. Hence, limiting brain inflammatory response and improving the resolution of inflammation could be particularly of interest to prevent these alterations. Dietary n-3 long chain polyunsaturated fatty acids (LC-PUFAs) and low molecular weight peptides are good candidates because of their immunomodulatory and proresolutive properties. These compounds are present in a fish hydrolysate derived from marine-derived byproducts. In this study, we compared the effect of an 18-day supplementation with this fish hydrolysate to a supplementation with docosahexaenoic acid (DHA) on lipopolysaccharide (LPS)-induced inflammation in mice. In response to peripherally injected LPS, the fish hydrolysate supplementation decreased the hippocampal mRNA expression of the proinflammatory cytokines IL-6 (p < 0.001), IL-1β (p = 0.0008) and TNF-α (p < 0.0001), whereas the DHA supplementation reduced only the expression of IL-6 (p = 0.004). This decline in proinflammatory cytokine expressions was associated with an increase in the protein expression of IκB (p = 0.014 and p = 0.0054 as compared to the DHA supplementation and control groups, respectively) and to a modulation of microglial activation markers in the hippocampus. The beneficial effects of the fish hydrolysate could be due in part to the switch of the hippocampal oxylipin profile towards a more anti-inflammatory profile as compared to the DHA supplementation. Thus, the valorization of fish byproducts seems very attractive to prevent and counteract neuroinflammation. 相似文献
30.
Juliana Chen Solne Bertrand Olivier Galy David Raubenheimer Margaret Allman-Farinelli Corinne Caillaud 《Nutrients》2021,13(5)
The food environment in New Caledonia is undergoing a transition, with movement away from traditional diets towards processed and discretionary foods and beverages. This study aimed to develop an up-to-date food composition database that could be used to analyze food and nutritional intake data of New Caledonian children and adults. Development of this database occurred in three phases: Phase 1, updating and expanding the number of food items to represent current food supply; Phase 2, refining the database items and naming and assigning portion size images for food items; Phase 3, ensuring comprehensive nutrient values for all foods, including saturated fat and total sugar. The final New Caledonian database comprised a total of 972 food items, with 40 associated food categories and 25 nutrient values and 615 items with portion size images. To improve the searchability of the database, the names of 593 food items were shortened and synonyms or alternate spelling were included for 462 foods. Once integrated into a mobile app-based multiple-pass 24-h recall tool, named iRecall.24, this country-specific food composition database would support the assessment of food and nutritional intakes of families in New Caledonia, in a cross-sectional and longitudinal manner, and with translational opportunities for use across the wider Pacific region. 相似文献