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121.
Interaction among smoking status,single nucleotide polymorphisms and markers of systemic inflammation in healthy individuals 下载免费PDF全文
Thitiya Luetragoon Lars E. Rutqvist Orathai Tangvarasittichai Bengt‐Åke Andersson Sture Löfgren Kanchana Usuwanthim Nongnit L. Lewin 《Immunology》2018,154(1):98-103
Cigarette smoke contains toxic and carcinogenic substances that contribute to the development of cancer and various diseases. Genetic variation might be important, because not all smokers develop smoking‐related disease. The current study addressed the possible interactions among selected single nucleotide polymorphisms (SNPs) in genes related to systemic inflammation, smoking status, the levels of circulating immune response cells and plasma biomarkers of systemic inflammation. Sixty‐four healthy blood donors were recruited, 31 of whom were current smokers and 33 were never‐users of tobacco products, references. Compared to references, the smokers showed significantly increased levels of circulating total white blood cells, lymphocytes, monocytes, neutrophils, basophils and C‐reactive protein (CRP). Smokers also more frequently exhibited circulating cell phenotypes that are associated with an immunocompromised state: CD8dim cells in the lymphocyte group, CD13+ CD11+, CD13+ CD14+, CD13+ CD56+ cells in the monocyte group and CD13+ CD11+, CD13+ CD56+ cells in the neutrophil group. We observed an interaction among SNPs, smoking status and some of the studied biomarkers. The average plasma CRP level was significantly higher among the smokers, with the highest level found among those with the CRP rs1800947 CC genotype. Additionally, an increased CD8+ GZB+ cells in the CD8dim group were found among smokers with the GZB rs8192917 AA genotype. Thus, smoking appears to be associated with systemic inflammation and increased levels of circulating immunosuppressive cells. The extent of these effects was associated with SNPs among the smokers. This observation may contribute to a better understanding of the genetic susceptibility of smoking‐related disease and the variations observed in clinical outcomes. 相似文献
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Are lymph node micrometastases of any clinical significance in dukes stages A and B colorectal cancer? 总被引:10,自引:4,他引:10
Dr. Åke Öberg M.D. Roger Stenling M.D. Ph.D. Björn Tavelin B.Sc. Gudrun Lindmark M.D. Ph.D. 《Diseases of the colon and rectum》1998,41(10):1244-1249
PURPOSE: The aim was to investigate the significance of lymph node micrometastases in Dukes Stages A and B colorectal cancer. METHODS: Archival specimens were examined from 147 patients (96 colon, 51 rectum; 44 Stage A, 103 Stage B) who had surgery between 1987 and 1994. One lymph node section from each node (colon, 1–11; median, 4; rectum, 1–15; median, 3) was examined with use of an anticytokeratin antibody. RESULTS: Forty-seven (32 percent) patients had micrometastases. At follow-up in June 1996, 23 patients had died of cancer or with known tumor relapse, after a median time of 28 (range, 5–67) months; 8 of 47 (17 percent) patients had micrometastases, 15 of 100 (15 percent) did not. No statistically significant differences were observed according to micrometastases when the results were analyzed with respect to Dukes stage or survival time. The median survival time of living patients with micrometastases was 48 (range, 18–97) months, and for patients without micrometastases, 48 (range, 19–111) months. Six of 96 living patients had a tumor relapse; three of these displayed micrometastases. CONCLUSION: Lymph node micrometastases are not a useful prognostic marker in Dukes Stages A and B and do not imply different strategies for additional therapy or follow-up.This study was supported by the Swedish Cancer Foundation (Project No 2520-B96-10XCC, Project No 3453-B97-05XBB).Read at the Second Surgical Week, Västerås, Sweden, August 18 to 22, 1997. 相似文献
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Anna Barlind Niklas Karlsson N. David Åberg Thomas Björk-Eriksson Klas Blomgren Jörgen Isgaard 《Growth hormone & IGF research》2010,20(1):49-54
ObjectiveRadiation therapy (RT) to the brain is often used in the treatment of children with different types of malignant diseases affecting the brain. However, RT in childhood may also have severe side effects including impaired brain maturation and intellectual development. For childhood cancer survivors these adverse effects of RT can cause lifelong disability and suffering. Therefore, there is an unmet need to limit late effects after RT. Precursor cells in the subgranular zone of the dentate gyrus (DG) in the hippocampus are particularly sensitive to irradiation (IR). This may be of significance as newly generated neurons in the DG are important for memory and learning. GH secretagogues (GHS) have previously been shown to promote neurogenesis and to have neuroprotective effects. In addition, several parts of the brain, including the hippocampus, have been shown to express the GHS receptor 1a (GHS-R1a). The aim of this study was to evaluate the potential effect of the GHS hexarelin on proliferation and survival of progenitor cells in the hippocampus after brain IR in a mouse model.DesignIn the present study, 10-day-old male mice received 6 Gy cranial IR. Non-irradiated sham animals were used as controls. We treated one group of irradiated and one sham group with hexarelin (100 μg/kg/day) for 28 days and used immunohistochemical labeling of bromo-deoxy uridine (BrdU) and phospho-histone H3 of the granular cell layer of the DG to evaluate proliferation and cell survival after IR at postnatal day ten.ResultsOur results show that hexarelin significantly increased the number of BrdU-positive cells in the granule cell layer by approximately 50% compared to controls.ConclusionThe increased number of BrdU-positive cells in the granule cell layer suggests a partial restoration in the pool of proliferating cells by hexarelin after IR. 相似文献
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Björk C Nenonen H Giwercman A Bergman Å Rylander L Giwercman YL 《Reproductive toxicology (Elmsford, N.Y.)》2011,32(3):293-297
Recently, the effect of exposure to persistent organic pollutants (POPs) on sperm concentration was only seen in men with a short androgen receptor (AR) gene CAG repeat. In order to investigate whether these effects could be observed also in vitro, we tested the impact of 2,2′,4,4′,5,5′-hexachlorobiphenyl (CB-153) and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (4,4′-DDE) on 5α-dihydrotestosterone activated ARs containing 16, 22 and 28 CAG repeats, respectively. Single exposure to 4,4′-DDE had the most pronounced effect on the AR activity containing 16 CAG repeats, whereas 28 CAG was the most sensitive variant when a mixture of the two compounds was added. Thus, our in vitro results have confirmed the in vivo data indicating a CAG repeat length dependent effect of endocrine disrupters on the AR activity. 相似文献
128.
Engman J ?hs F Furmark T Linnman C Pissiota A Appel L Frans ? L?ngstr?m B Fredrikson M 《European neuropsychopharmacology》2012,22(8):562-568
The substance P/neurokinin 1 (SP/NK1) system has been implicated in the processing of negative affect. Its role seems complex and findings from animal studies have not been easily translated to humans. Brain imaging studies on NK1 receptor distribution in humans have revealed an abundance of receptors in cortical, striatal and subcortical areas, including the amygdala. A reduction in NK1 receptors with increasing age has been reported in frontal, temporal, and parietal cortices, as well as in hippocampal areas. Also, a previous study suggests sex differences in cortical and subcortical areas, with women displaying fewer NK1 receptors. The present PET study explored NK1 receptor availability in men (n=9) and women (n=9) matched for age varying between 20 and 50years using the highly specific NK1 receptor antagonist [(11)C]GR205171 and a reference tissue model with cerebellum as the reference region. Age by sex interactions in the amygdala and the temporal cortex reflected a lower NK1 receptor availability with increasing age in men, but not in women. A general age-related decline in NK1 receptor availability was evident in the frontal, temporal, and occipital cortices, as well as in the brainstem, caudate nucleus, and thalamus. Women had lower NK1 receptor availability in the thalamus. The observed pattern of NK1 receptor distribution in the brain might have functional significance for brain-related disorders showing age- and sex-related differences in prevalence. 相似文献
129.
Plyusnina A Krajinović LC Margaletić J Niemimaa J Nemirov K Lundkvist Å Markotić A Miletić-Medved M Avšič-Županc T Henttonen H Plyusnin A 《Journal of medical virology》2011,83(1):108-114
In Europe, Dobrava-Belgrade (DOBV), Saaremaa (SAAV), and Puumala (PUUV) viruses are known to cause hemorrhagic fever with renal syndrome (HFRS). All three hantaviruses are now found in Croatia. Lung tissue samples of 315 Apodemus mice trapped in 2003-2004 were screened for the presence of hantaviral N-Ag and 20 mice (6.3%) were found either strongly positive or weak/suspected-positive. Partial sequences of hantavirus M and S segments were recovered by RT-PCR from six mice and subjected to (phylo)genetic analysis that revealed the presence of four novel strains of DOBV and one of SAAV. Curiously, one of the newly described DOBV strains was found in Apodemus agrarius mouse, that is, not in the traditional host, A. flavicollis mice, suggesting a spillover event. S segment sequences recovered previously from HFRS cases [Markoti? et al., 2002] were confirmed as DOBV sequences; one of which appeared particularly close to the prototype Slovenian DOBV isolate. Taken together with earlier data on PUUV in Croatia, these results show a co-circulation of three European hantavirus pathogens in this country. So far, not a single SAAV sequence has been recovered from HFRS patients either in Croatia or neighboring Slovenia and Hungary nor in Slovakia suggesting a somewhat lower fequency of acute SAAV infection in humans in this part of Europe than for example in the Baltics. 相似文献
130.
Huffman JE Knezevic A Vitart V Kattla J Adamczyk B Novokmet M Igl W Pucic M Zgaga L Johannson Å Redzic I Gornik O Zemunik T Polasek O Kolcic I Pehlic M Koeleman CA Campbell S Wild SH Hastie ND Campbell H Gyllensten U Wuhrer M Wilson JF Hayward C Rudan I Rudd PM Wright AF Lauc G 《Human molecular genetics》2011,20(24):5000-5011
The majority of human proteins are post-translationally modified by covalent addition of one or more complex oligosaccharides (glycans). Alterations in glycosylation processing are associated with numerous diseases and glycans are attracting increasing attention both as disease biomarkers and as targets for novel therapeutic approaches. Using a recently developed high-throughput high-performance liquid chromatography (HPLC) analysis method, we have reported, in a pilot genome-wide association study of 13 glycan features in 2705 individuals from three European populations, that polymorphisms at three loci (FUT8, FUT6/FUT3 and HNF1A) affect plasma levels of N-glycans. Here, we extended the analysis to 33 directly measured and 13 derived glycosylation traits in 3533 individuals and identified three novel gene association (MGAT5, B3GAT1 and SLC9A9) as well as replicated the previous findings using an additional European cohort. MGAT5 (meta-analysis association P-value = 1.80 × 10(-10) for rs1257220) encodes a glycosyltransferase which is known to synthesize the associated glycans. In contrast, neither B3GAT1 (rs7928758, P = 1.66 × 10(-08)) nor SLC9A9 (rs4839604, P = 3.50 × 10(-13)) had previously been associated functionally with glycosylation of plasma proteins. Given the glucuronyl transferase activity of B3GAT1, we were able to show that glucuronic acid is present on antennae of plasma glycoproteins underlying the corresponding HPLC peak. SLC9A9 encodes a proton pump which affects pH in the endosomal compartment and it was recently reported that changes in Golgi pH can impair protein sialylation, giving a possible mechanism for the observed association. 相似文献