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991.
Olivero-David R Schultz-Moreira A Vázquez-Velasco M González-Torres L Bastida S Benedí J Sanchez-Reus MI González-Muñoz MJ Sánchez-Muniz FJ 《The British journal of nutrition》2011,106(10):1476-1486
Some seaweeds exert antioxidant and hypocholesterolaemic properties. The effects of diets including restructured meats (RM) containing Wakame (W) or Nori (N) algae on arylesterase (AE) activity and lipoprotein concentration and composition were tested. In the present study, six groups of ten male growing Wistar rats each were fed a mix of 85?% AIN-93M diet and 15?% freeze-dried RM for 35?d. The control group (C) consumed control RM, the W and N groups consumed RM with 5?% W and 5?% N, respectively. The cholesterol-enriched C (CC), W (CW) and N (CN) groups consumed their corresponding basal diets with supplementary cholesterol (2·43?%) and cholic acid (0·49?%). Cholesterol in the diet induced lower (P?0·001) growth ratios. Both W and N diets significantly increased AE activity. VLDL-cholesterol values were lower in N rats than in W rats. AE activity increased (P?0·001) in CC and CW rats but not in CN rats compared with their corresponding counterparts. AE was lower (P?0·05) in the CN group than in the CC and CW groups. The CN diet partially blocked (P?0·001) the hypercholesterolaemic induction observed in CC and CW diets and reduced TAG levels (at least P?0·05) with respect to those of CC rats. Although dietary cholesterol supplementation increased total cholesterol, VLDL-cholesterol and (intermediate-density lipoprotein+LDL)-cholesterol (all P?0·001) in all rats, the CN diet moderately improved the lipoprotein profile of hypercholesterolaemic rats. Changes in AE activity and plasma cholesterol in CN rats but not in CW rats suggest a possible relationship between the two parameters. It is concluded that inclusion of RM enriched with N may be used in hypercholesterolaemic diets to improve lipoprotein metabolism. 相似文献
992.
Drug resistance is problematic in microbial disease, viral disease and cancer. Understanding at the outset that resistance will impact the effectiveness of any new drug that is developed for these disease categories is imperative. In this Feature, we detail approaches that have been taken with selected drug targets to reduce the susceptibility of new drugs to resistance mechanisms. We will also define the concepts of robust drugs and resilient targets, and discuss how the design of robust drugs and the selection of resilient targets can lead to successful strategies for combating resistance. 相似文献
993.
Human Langerhans cells induce distinct IL-22-producing CD4+ T cells lacking IL-17 production
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Hideki Fujita Kristine E. Nograles Toyoko Kikuchi Juana Gonzalez John A. Carucci James G. Krueger 《Proceedings of the National Academy of Sciences of the United States of America》2009,106(51):21795-21800
IL-22 is a cytokine that acts mainly on epithelial cells. In the skin, it mediates keratinocyte proliferation and epidermal hyperplasia and is thought to play a central role in inflammatory diseases with marked epidermal acanthosis, such as psoriasis. Although IL-22 was initially considered a Th17 cytokine, increasing evidence suggests that T helper cells can produce IL-22 even without IL-17 expression. In addition, we have shown the existence of this unique IL-22-producing T cell in normal skin and in the skin of psoriasis and atopic dermatitis patients. In the present study, we investigated the ability of cutaneous resident dendritic cells (DCs) to differentiate IL-22-producing cells. Using FACS, we isolated Langerhans cells (LCs; HLA-DR+CD207+ cells) and dermal DCs (HLA-DRhiCD11c+BDCA-1+ cells) from normal human epidermis and dermis, respectively. Both LCs and dermal DCs significantly induced IL-22-producing CD4+ and CD8+ T cells from peripheral blood T cells and naive CD4+ T cells in mixed leukocyte reactions. LCs were more powerful in the induction of IL-22-producing cells than dermal DCs. Moreover, in vitro-generated LC-type DCs induced IL-22-producing cells more efficiently than monocyte-derived DCs. The induced IL-22 production was more correlated with IFN-γ than IL-17. Surprisingly, the majority of IL-22-producing cells induced by LCs and dermal DCs lacked the expression of IL-17, IFN-γ, and IL-4. Thus, LCs and dermal DCs preferentially induced helper T cells to produce only IL-22, possibly “Th22” cells. Our data indicate that cutaneous DCs, especially LCs, may control the generation of distinct IL-22 producing Th22 cells infiltrating into the skin. 相似文献
994.
Goday-Arno A Cerda-Esteva M Flores-Le-Roux JA Chillaron-Jordan JJ Corretger JM Cano-Pérez JF 《Clinical endocrinology》2009,71(1):110-114
Background Thyroid disorders are frequent in patients with Down syndrome (DS). It is well-known that the prevalence of hypothyroidism is high but data on hyperthyroidism are scarce.
Objectives To assess the prevalence, aetiology, clinical characteristics, evolution and treatment of hyperthyroidism in a population with DS attending a specialized medical centre.
Methods Data were gathered by systematic review of 1832 medical records from the Catalan DS Foundation, in Spain, registered between January 1991 and February 2006. Patients with the diagnosis of hyperthyroidism were identified and data on clinical features, physical examination, laboratory and imaging tests, treatment and evolution were collected.
Results Twelve patients with hyperthyroidism were recorded (6·5 cases/1000 patients with DS). There were 5 males and 7 females, with a mean age at diagnosis of 16·8 years. The most common presenting symptoms were decreased heat tolerance, sweating, increased irritability and weight loss. All patients had diffuse goitre at physical examination and two patients presented with exophthalmia. Clinical diagnosis was confirmed biochemically. Thyroid-stimulating immunoglobulin levels were raised (mean 128·1 U/l) and imaging tests confirmed the diagnosis of Graves' disease in all cases. Patients started treatment with carbimazole at diagnosis and after a mean period of 40 months without clinical remission, they required definitive therapy with radioactive iodine. Subjects developed hypothyroidism after radio-iodine therapy and replacement therapy with levothyroxine was necessary.
Conclusions Hyperthyroidism is more prevalent in patients with DS than in the general population and has no gender predominance. It is caused mainly by Graves' disease. Anti-thyroid drugs were not effective in achieving remission and radioactive iodine as a definitive treatment was required in all cases. 相似文献
Objectives To assess the prevalence, aetiology, clinical characteristics, evolution and treatment of hyperthyroidism in a population with DS attending a specialized medical centre.
Methods Data were gathered by systematic review of 1832 medical records from the Catalan DS Foundation, in Spain, registered between January 1991 and February 2006. Patients with the diagnosis of hyperthyroidism were identified and data on clinical features, physical examination, laboratory and imaging tests, treatment and evolution were collected.
Results Twelve patients with hyperthyroidism were recorded (6·5 cases/1000 patients with DS). There were 5 males and 7 females, with a mean age at diagnosis of 16·8 years. The most common presenting symptoms were decreased heat tolerance, sweating, increased irritability and weight loss. All patients had diffuse goitre at physical examination and two patients presented with exophthalmia. Clinical diagnosis was confirmed biochemically. Thyroid-stimulating immunoglobulin levels were raised (mean 128·1 U/l) and imaging tests confirmed the diagnosis of Graves' disease in all cases. Patients started treatment with carbimazole at diagnosis and after a mean period of 40 months without clinical remission, they required definitive therapy with radioactive iodine. Subjects developed hypothyroidism after radio-iodine therapy and replacement therapy with levothyroxine was necessary.
Conclusions Hyperthyroidism is more prevalent in patients with DS than in the general population and has no gender predominance. It is caused mainly by Graves' disease. Anti-thyroid drugs were not effective in achieving remission and radioactive iodine as a definitive treatment was required in all cases. 相似文献
995.
Normal development of spinal axons in early embryo stages and posterior locomotor function is independent of GAL‐1
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Juana M. Pasquini Francisco J. Barrantes Héctor R. Quintá 《The Journal of comparative neurology》2017,525(13):2861-2875
It was recently described that Galectin‐1 (Gal‐1) promotes axonal growth after spinal cord injury. This effect depends on protein dimerization, since monomeric Gal‐1 fails to stimulate axonal re‐growth. Gal‐1 is expressed in vivo at concentrations that favor the monomeric species. The aim of the present study is to investigate whether endogenous Gal‐1 is required for spinal axon development and normal locomotor behavior in mice. In order to characterize axonal development, we used a novel combination of 3‐DISCO technique with 1‐photon microscopy and epifluorescence microscopy under high power LED illumination, followed by serial image section deconvolution and 3‐D reconstruction. Cleared whole lgals‐1‐/‐ embryos were used to analyze the 3‐D cytoarchitecture of motor, commissural, and sensory axons. This approach allowed us to evaluate axonal development, including the number of fibers, fluorescence density of the fiber tracts, fiber length as well as the morphology of axonal sprouting, deep within the tissue. Gal‐1 deficient embryos did not show morphological/anatomical alterations in any of the axonal populations and parameters analyzed. In addition, specific guidance receptor PlexinA4 did not change its axonal localization in the absence of Gal‐1. Finally, Gal‐1 deficiency did not change normal locomotor activity in post‐natal animals. Taken together, our results show that development of spinal axons as well as the locomotor abilities observed in adult mice are independent of Gal‐1. Supporting our previous observations, the present study further validates the use of lgals‐1‐/‐ mice to develop spinal cord‐ or traumatic brain injury models for the evaluation of the regenerative action of Gal‐1. 相似文献
996.
Marta Mellai Laura Annovazzi Rebecca Senetta Carmine Dell’Aglio Marta Mazzucco Paola Cassoni Davide Schiffer 《Journal of neuro-oncology》2017,131(2):213-222
The diagnosis of 206 low and high grade adult gliomas, including 40 oligoastrocytomas, was revised based on the immunohistochemical reactivity for the ATRX protein, IDH1/2 mutation status and 1p/19q chromosomal status. All oligodendrogliomas kept the initial diagnosis. Astrocytomas did not change diagnosis in 30 of 36 cases (83.3?%); four of 36 (11.1?%) cases were reclassified as oligodendroglioma, one (2.8?%) as DNT and the other (2.8?%) as reactive gliosis. Oligoastrocytomas changed diagnosis in 35 of 40 (87.5?%) cases, being reclassified 22 of 40 (55?%) as astrocytoma, 11 of 40 (27.5?%) as oligodendroglioma and two of 40 (5?%) as reactive gliosis. Four (10?%) remained unclassifiable. In one case only (2.5?%), the diagnosis of oligoastrocytoma could not be excluded since tumor astrocytes and tumor oligodendrocytes coexisted in mixed tumor areas. In the GBM tumor subgroup, GBMO disappeared because they were not substantiated by molecular genetics. Pilocytic astrocytomas retained ATRX expression. Loss of nuclear ATRX protein expression was strongly associated to IDH1/2 mutations (p?=?0.0001) and mutually exclusive with total 1p/19q co-deletion (p?=?0.0001). In astrocytic tumors, loss of immunoreactivity for the ATRX protein was significantly associated to the ALT phenotype (p?=?0.0003). The constitutive ATRX expression in microglia/macrophages may be misleading, especially in the identification of an oligodendroglial tumor infiltration. Of paramount importance in the recognition of oligodendroglial and astrocytic tumor cells were the double immunostainings for ATRX/GFAP, ATRX/IDH1R132H, ATRX/Iba-1 and ATRX/CD68. 相似文献
997.
998.
Eva Pros Juana Fernández‐Rodríguez Belén Canet Llúcia Benito Aurora Sánchez Ana Benavides Feliciano J. Ramos María Asunción López‐Ariztegui Gabriel Capellá Ignacio Blanco Eduard Serra Conxi Lázaro 《Human mutation》2009,30(3):454-462
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder affecting 1:3,500 individuals. Disease expression is highly variable and complications are diverse. However, currently there is no specific treatment for the disease. NF1 is caused by mutations in the NF1 gene, approximately 2.1% of constitutional mutations identified in our population are deep intronic mutations producing the insertion of a cryptic exon into the mature mRNA. We used antisense morpholino oligomers (AMOs) to restore normal splicing in primary fibroblast and lymphocyte cell lines derived from six NF1 patients bearing three deep intronic mutations in the NF1 gene (c.288+2025T>G, c.5749+332A>G, and c.7908‐321C>G). AMOs were designed to target the newly created 5′ splice sites to prevent the incorporation of cryptic exons. Our results demonstrate that AMO treatment effectively restored normal NF1 splicing at the mRNA level for the three mutations studied in the different cell lines analyzed. We also found that AMOs had a rapid effect that lasted for several days, acting in a sequence‐specific manner and interfering with the splicing mechanism. Finally, to test whether the correction of aberrant NF1 splicing also restored neurofibromin function to wild‐type levels, we measured the amount of Ras‐GTP after AMO treatment in primary fibroblasts. The results clearly show an AMO‐dependent decrease in Ras‐GTP levels, which is consistent with the restoration of neurofibromin function. To our knowledge this is the first time that an antisense technique has been usedsuccessfully to correct NF1 mutations opening the possibility of a therapeutic strategy for this type of mutation not only for NF1 but for other genetic disorders. Hum Mutat 30, 454–462, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
999.
Fèlix Junyent Juana Utrera Antoni Camins Mercè Pallàs Rafael Romero Carme Auladell 《Neuroscience letters》2009
Taurine is one of the most abundant free amino acids in the mammalian central nervous system, where it is crucial for proper development. Moreover, taurine has been related with epilepsy, as it can reduce or prevent seizures. It is also a neuroprotectant in other experimental conditions. Glial cultures were analysed to determine the changes in taurine synthesis and traffic that occur in a more differentiated state of these cells. The cultures were treated with 8-Br-cAMP, an analogue of cAMP that induces differentiation in astrocytes. We observed an increase in immunoreactivity for GFAP, as well as an alteration in uptake-release kinetics in these cells. Moreover, we noted an increase in taurine levels and in cysteine sulfinic decarboxylase, which is the rate-limiting enzyme in taurine synthesis. The data indicate that taurine synthesis and traffic kinetics vary according to the differentiation state of the astrocytes. Thus, our results highlight the importance of astrocytes in modulating taurine levels in the brain. 相似文献
1000.