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12.
干扰素γ(IFNγ)又称免疫干扰素,其抗病毒活性较低,免疫调节和抗细胞增殖作用较强,是一种强的巨噬细胞、NK细胞、血管内皮细胞活化剂。IFNγ增强抗原提呈,活化T淋巴细胞,与多种致炎因子相互作用,促进粥样病变处炎症反应,加重病变进展。作为脂质代谢相关酶的调节因子,IFNγ诱导泡沫细胞形成,并活化内皮细胞促进动脉粥样硬化。但也有研究显示,它可影响一些脂质受体抑制泡沫细胞形成,并减少平滑肌细胞增殖而对动脉粥样硬化形成起保护作用。 相似文献
13.
G B Kovachich 《Neuroscience letters》1985,58(2):245-250
The effect of extracts from rat cerebral cortex was examined on the stability of norepinephrine-HC1 (NE) in 16 mM Na-phosphate buffer, pH 7.4, at 37 degrees C. The autoxidation products of NE were detected spectrophotometrically at 480 nm. Dialysed samples from a synaptosomal preparation and from the 100,000 g supernatant of a crude homogenate were tested. Aliquots from these preparations, in the range of 0.005-5.0 or 0.01-10.0 micrograms protein/ml, respectively, produced up to 80-85% inhibition of the autoxidation of 100 microM NE for a period of at least 3 h. Similar results were obtained with albumin and ovalbumin at 10- and 10(3)-times higher concentrations, respectively. After the preparations were exposed to 0.1-1.0 mg 6-hydroxydopamine-HC1/mg protein for 5 min at 25 degrees C followed by rapid dialysis, the maximal inhibitory effect was reduced to between 95% to less than 5% of control values. The percent inactivation by a given quantity of 6-hydroxydopamine (6-OHDA) was inversely related to the potency of the untreated sample. Additional observations are presented which suggest that the destruction of the antioxidant activity is caused by breakdown products of 6-OHDA reacting with nucleophilic sites of the preparation. Similar inactivating substances are expected to be formed from other autoxidizing catecholamines, although at a slower rate. 相似文献
14.
Gaëlle Dzangué-Tchoupou Kuberaka Mariampillai Loïs Bolko Damien Amelin Wladimir Mauhin Aurélien Corneau Catherine Blanc Yves Allenbach Olivier Benveniste 《Autoimmunity reviews》2019,18(4):325-333
Background
Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.Objectives
Our aim was to deepen our understanding of the immune mechanisms involved in inclusion body myositis and identify specific biomarkers.Methods
Using a panel of thirty-six markers and mass cytometry, we performed deep immune profiling of peripheral blood cells from inclusion body myositis patients and healthy donors, divided into two cohorts: test and validation cohorts. Potential biomarkers were compared to myositis controls (anti-Jo1-, anti-3-hydroxyl-3-methylglutaryl CoA reductase-, and anti-signal recognition particle-positive patients).Results
Unsupervised analyses revealed substantial changes only within CD8+ cells. We observed an increase in the frequency of CD8+ cells that expressed high levels of T-bet, and containing mainly both effector and terminally differentiated memory cells. The senescent marker CD57 was overexpressed in CD8+T-bet+ cells of inclusion body myositis patients. As expected, senescent CD8+T-bet+ CD57+ cells of both patients and healthy donors were CD28nullCD27nullCD127null. Surprisingly, non-senescent CD8+T-bet+ CD57- cells in inclusion body myositis patients expressed lower levels of CD28, CD27, and CD127, and expressed higher levels of CD38 and HLA-DR compared to healthy donors. Using classification and regression trees alongside receiver operating characteristics curves, we identified and validated a frequency of CD8+T-bet+ cells >51.5% as a diagnostic biomarker specific to inclusion body myositis, compared to myositis control patients, with a sensitivity of 94.4%, a specificity of 88.5%, and an area under the curve of 0.97.Conclusion
Using a panel of thirty-six markers by mass cytometry, we identify an activated cell population (CD8+T-bet+ CD57- CD28lowCD27lowCD127low CD38+ HLA-DR+) which could play a role in the physiopathology of inclusion body myositis, and identify CD8+T-bet+ cells as a predominant biomarker of this disease. 相似文献15.
Alyce C. Russell Agnieszka Kepka Irena Trbojević-Akmačić Ivo Ugrina Manshu Song Jennie Hui Michael Hunter Simon M. Laws Gordan Lauc Wei Wang 《Immunobiology》2019,224(1):110-115
Background
Increased body fat may be associated with an increased risk of developing an underlying pro-inflammatory state, thus leading to greater risk of developing certain chronic conditions. Immunoglobulin G has the ability to exert both anti- and pro-inflammatory effects, and the N-glycosylation of the fragment crystallisable portion is involved in mediating this process. Body mass index, a rudimentary yet gold standard indication for body fat, has been shown to be associated with agalactosylated immunoglobulin G N-glycans.Aim
We aimed to determine the association between increased body fat and the immunoglobulin G glycosylation features, comparing body mass index to other measures of body fat distribution.Methods
We investigated a sample of 637 community-based 45–69?year olds, with mixed phenotypes, residing in Busselton, Western Australia. Body mass index and the waist-to-hip and waist-to-height ratios were calculated using anthropometry, while dual-energy x-ray absorptiometry was performed to gain an accurate measure of total and area specific body fat. Serum immunoglobulin GN-glycans were analysed by ultra-performance liquid chromatography.Results
Twenty-two N-glycan peaks were found to be associated with at least one of the fat measures. While the previous association of body mass index to agalactosylated immunoglobulin G was replicated, measures of central adiposity explained the most variation in the immunoglobulin G glycome.Conclusion
Central adiposity is associated with an increased pro-inflammatory fraction of immunoglobulin G, suggesting that the android/gynoid ratio or waist-to-height ratio instead be considered when controlling for adiposity in immunoglobulin G glycome biomarker studies. 相似文献16.
Bradley J. Buck Ilan A. Kerman Paul R. Burghardt Lauren G. Koch Steven L. Britton Huda Akil Stanley J. Watson 《Neuroscience letters》2007
Metabolic syndrome is characterized by obesity, elevated blood pressure (BP), insulin resistance, and hypercholesterolemia. Recently an animal model of this disorder has been proposed in rats selectively bred based on their performance on a treadmill-running task. Accordingly, low capacity runner (LCR) rats exhibited all of the diagnostic criteria for metabolic syndrome, including elevated BP, as compared to their high capacity runner (HCR) counterparts [U. Wisløff, S.M. Najjar, O. Ellingsen, P.M. Haram, S. Swoap, Q. Al-Share, M. Fernstrom, K. Rezaei, S.J. Lee, L.G. Koch, S.L. Britton, Cardiovascular risk factors emerge after artificial selection for low aerobic capacity, Science 307 (2005) 418–420]. Previous studies have highlighted the importance of GABAergic neurotransmission in the medullary cardiovascular-regulatory areas in the central control of BP. Thus, we hypothesized a dysregulation in GABAergic transmission in the medullary cardiovascular-regulatory nuclei of LCR rats. To begin testing this hypothesis we carried out experiments examining expression of the GABA synthetic enzymes, GAD65 and GAD67, mRNAs in the two rat strains via radioactive in situ hybridization. Our results showed GAD65 and GAD67 mRNAs were widely expressed throughout the brainstem; quantification revealed increased GAD65 mRNA expression in LCR animals in the caudal nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (VLM) as compared to HCR rats. Conversely, no differences in the expression of GAD67 were detected in these regions. These data are consistent with the notion of altered GABAergic neurotransmission in the NTS and VLM in metabolic syndrome, and point to the importance of these regions in cardiovascular regulation. 相似文献
17.
Role of double-stranded RNA and Npro of classical swine fever virus in the activation of monocyte-derived dendritic cells 总被引:2,自引:0,他引:2
Classical swine fever virus (CSFV) is a noncytopathogenic (ncp) positive-sense RNA virus that replicates in myeloid cells including macrophages and dendritic cells (DC). The virus does not induce type I interferon (IFN-alpha/beta), which in macrophages has been related to the presence of the viral Npro gene. In the present work, the role of viral double-stranded (ds)RNA and Npro in the virus-host cell interaction has been analyzed. Higher levels of detectable dsRNA were produced by a genetically engineered cytopathogenic (cp) CSFV compared with ncp CSFV, and cp CSFV induced IFN-alpha/beta in PK-15 cells. With DC, there was only a small difference in the levels of dsRNA between the cp and ncp viruses, and no IFN-alpha/beta was produced. However, the cp virus induced a higher degree of DC maturation, in terms of CD80/86 and MHC II expression. Npro deletion mutants induced an increase in DC maturation and IFN-alpha/beta production-for both ncp and cp viruses-despite reduced replication efficiency in the DC. Deletion of Npro did not influence dsRNA levels, indicating that the interference was downstream of dsRNA turnover regulation. In conclusion, the capacity of CSFV to replicate in myeloid DC, and prevent IFN-alpha/beta induction and DC maturation, requires both regulated dsRNA levels and the presence of viral Npro. 相似文献
18.
Min-Seok Rha Hye Won Jeong Jae-Hoon Ko Seong Jin Choi In-Ho Seo Jeong Seok Lee Moa Sa A Reum Kim Eun-Jeong Joo Jin Young Ahn Jung Ho Kim Kyoung-Ho Song Eu Suk Kim Dong Hyun Oh Mi Young Ahn Hee Kyoung Choi Ji Hoon Jeon Jae-Phil Choi Eui-Cheol Shin 《Immunity》2021,54(1):44-52.e3
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19.
磷脂酶C-γ1在人胚胎脊髓中的表达变化 总被引:1,自引:0,他引:1
为了了解磷脂酶C-γ1(PLC-γ1)的发育表达变化特点,本研究采用免疫组织化学方法检测不同发育时期的人胚胎脊髓中PLC-γ1的表达及变化。结果显示:PLC-γ1在人胚胎脊髓3周到7个月的整个发育过程中均有表达,在发育早期阳性反应可见于神经管内、外界膜,随着套层、边缘层的形成,神经上皮层、套层中均可见到PLC-γ1阳性反应物,且翼板阳性细胞较基板密集;套层阳性细胞在8、9周时达到高峰,随后开始逐渐减少。3个月时边缘层出现散在的阳性细胞,并随着脊髓的发育而逐渐增多。以上结果提示,PLC-γ1及其与PLC-γ1相关的细胞信号通路对人胚胎脊髓的发育可能发挥了重要的生物学作用。 相似文献
20.
Benzodiazepines both enhance gamma-aminobutyrate responses and decrease calcium action potentials in guinea-pig myenteric neurones 总被引:1,自引:0,他引:1
The effect of two benzodiazepines, midazolam and diazepam, was studied in guinea-pig myenteric neurones, using intracellular recording techniques. Both these benzodiazepines (100-300 pM) potentiated the rapidly desensitizing, bicuculline-sensitive depolarization, induced by alpha-aminobutyrate ionophoresis. Concentrations of midazolam and diazepam higher than 100 nM depressed the gamma-aminobutyrate-induced depolarization. The potentiating effect of the benzodiazepines was reversibly abolished by Ro 15-1788 (1-100 nM) and by pentylenetetrazol (100 microM). A second effect of midazolam and diazepam (100-300 pM) was a reversible depression of the amplitude and duration of the directly evoked action potential in 29% of neurones, without affecting membrane potential or conductance. The effect was very marked when electrodes were filled with CsCl, and was also seen in the presence of tetrodotoxin. In some but not all of these neurones, the amplitude and duration of the action potentials was reduced also by gamma-aminobutyrate (1-10 microM). Ro 15-1788 and pentylenetetrazol reversibly abolished the effect of benzodiazepines on the action potential, but not that of gamma-aminobutyrate. Thus, benzodiazepines have two effects on myenteric neurones. The first is an enhancement of the gamma-aminobutyrate response (activation of Cl conductance); the second is a depression of the calcium action potential, which appears to be independent of gamma-aminobutyrate. 相似文献