全文获取类型
收费全文 | 530篇 |
免费 | 53篇 |
专业分类
儿科学 | 35篇 |
妇产科学 | 12篇 |
基础医学 | 54篇 |
口腔科学 | 3篇 |
临床医学 | 81篇 |
内科学 | 95篇 |
皮肤病学 | 9篇 |
神经病学 | 34篇 |
特种医学 | 43篇 |
外科学 | 36篇 |
综合类 | 15篇 |
预防医学 | 42篇 |
眼科学 | 2篇 |
药学 | 65篇 |
1篇 | |
中国医学 | 1篇 |
肿瘤学 | 55篇 |
出版年
2021年 | 11篇 |
2020年 | 5篇 |
2019年 | 5篇 |
2018年 | 7篇 |
2017年 | 4篇 |
2016年 | 12篇 |
2015年 | 15篇 |
2014年 | 12篇 |
2013年 | 12篇 |
2012年 | 21篇 |
2011年 | 22篇 |
2010年 | 20篇 |
2009年 | 22篇 |
2008年 | 11篇 |
2007年 | 16篇 |
2006年 | 24篇 |
2005年 | 20篇 |
2004年 | 25篇 |
2003年 | 14篇 |
2002年 | 11篇 |
2001年 | 14篇 |
2000年 | 21篇 |
1999年 | 11篇 |
1998年 | 11篇 |
1997年 | 23篇 |
1996年 | 11篇 |
1995年 | 9篇 |
1994年 | 13篇 |
1993年 | 8篇 |
1992年 | 6篇 |
1991年 | 12篇 |
1990年 | 7篇 |
1989年 | 14篇 |
1988年 | 18篇 |
1987年 | 11篇 |
1986年 | 7篇 |
1985年 | 8篇 |
1984年 | 7篇 |
1982年 | 7篇 |
1981年 | 9篇 |
1980年 | 4篇 |
1977年 | 10篇 |
1976年 | 5篇 |
1974年 | 7篇 |
1972年 | 4篇 |
1971年 | 3篇 |
1966年 | 3篇 |
1965年 | 3篇 |
1964年 | 4篇 |
1963年 | 3篇 |
排序方式: 共有583条查询结果,搜索用时 15 毫秒
1.
Different modulation by histamine of IL-4 and interferon-gamma (IFN-γ) release according to the phenotype of human Th0, Th1 and Th2 clones 下载免费PDF全文
Histamine, an important inflammatory mediator in allergic diseases and asthma, has been reported to have modulator effects on T cells, suggesting that the bronchial microenvironment may regulate the function of resident T cells. We examined the effect of histamine on the release of the Th2-associated cytokines IL-4 and IL-5 and the Th1-associated cytokine IFN-γ by 30 CD4+ T cell clones from peripheral blood or bronchial biopsy of one atopic subject. Based on the IL-4/IFN-γ ratio, the clones were ascribed to the Th2 (ratio >1), Th0 (ratio 0.1 and 1) or Th1 (ratio <0.1) phenotype. Histamine inhibited IFN-γ production by Th1-like cells (P<0.02, Kruskall–Wallis), especially from bronchial biopsy, but had no effect on IL-4 release. Regarding Th0 clones, histamine inhibited IL-4 production (P<0.02) in a dose-dependent manner and slightly inhibited IFN-γ production, but had no effect on Th2-like cells. Histamine had a heterogeneous and insignificant effect on IL-5 production. The H2-receptor antagonist ranitidine completely reversed the inhibition of IL-4 and IFN-γ production, whereas the agonist dimaprit mimicked this effect. In contrast, H1- and H3-receptor agonists and antagonists had no significant effect. These data demonstrate that histamine has different effects on IL-4 and IFN-γ release by T helper cells according to their phenotype via H2-receptors. This study extends the immunomodulatory effects of histamine which may contribute to the perpetuation of airway inflammation in asthma. 相似文献
2.
Human leukocyte antigen matching and fetal loss: results of a 10 year prospective study 总被引:6,自引:0,他引:6
Ober C; Hyslop T; Elias S; Weitkamp LR; Hauck WW 《Human reproduction (Oxford, England)》1998,13(1):33-38
The role that maternal and fetal human leukocyte antigen (HLA) genes play
in pregnancy is unknown, but it has been suggested that fetuses whose HLA
alleles do not differ from maternal alleles (i.e. histocompatible fetuses)
are more likely to be aborted than fetuses with HLA alleles that differ
from maternal alleles (i.e. histoincompatible fetuses). To elucidate the
role of HLA compatibility in pregnancy, we tested the hypothesis that
couples who match for HLA alleles or haplotypes would have reduced
fertility because only these couples could produce histocompatible fetuses.
We conducted a 10 year prospective study of HLA matching and pregnancy
outcome in 111 Hutterite couples, providing information on 251 pregnancies.
A logistic regression analysis was performed to determine the effects of
HLA matching at HLA regions and loci on pregnancy outcome (fetal loss
versus delivery). Significantly increased fetal loss rates were observed
among couples matching for the entire 16-locus haplotype (P = 0.002). Among
the individual loci, loss rates were increased among couples matching for
HLA-B (P = 0.019), HLA-C (P = 0.033) and the complement component, C4 (P =
0.043). We interpret these results as evidence that matching for the entire
16-locus haplotype and/or alleles at an HLA-B-linked locus confers
significant risk for fetal loss.
相似文献
3.
The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission 总被引:2,自引:5,他引:2
Murray A; Macpherson JN; Pound MC; Sharrock A; Youings SA; Dennis NR; McKechnie N; Linehan P; Morton NE; Jacobs PA 《Human molecular genetics》1997,6(2):173-184
Factors involved in the stability of trinucleotide repeats during
transmission were studied in 139 families in which a full mutation,
premutation or intermediate allele at either FRAXA or FRAXE was
segregating. The transmission of alleles at FRAXA, FRAXE and four
microsatellite loci were recorded for all individuals. Instability within
the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for
FRAXE) was extremely rare; only one example was observed, an increased in
size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in
the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were
unstably transmitted. Instability was more frequent for FRAXA intermediate
alleles that had a tract of pure CGG greater than 37 although instability
only occurred in two of 13 such transmissions: the changes observed were
limited to only one or two repeats. Premutation FRAXA alleles over 100
repeats expanded to a full mutation during female transmission in 100% of
cases, in agreement with other published series. There was no clear
correlation between haplotype and probability of expansion of FRAXA
premutations. Instability at FRAXA or FRAXE was more often observed in
conjunction with a second instability at an independent locus suggesting
genomic instability as a possible mechanism by which at least some FRAXA
and FRAXE mutations arise.
相似文献
4.
HAART improves prognosis in HIV-associated progressive multifocal leukoencephalopathy 总被引:5,自引:0,他引:5
Clifford DB Yiannoutsos C Glicksman M Simpson DM Singer EJ Piliero PJ Marra CM Francis GS McArthur JC Tyler KL Tselis AC Hyslop NE 《Neurology》1999,52(3):623-625
Introduction of highly active antiretroviral therapy (HAART) has been associated with many changes in the complications of human immunodeficiency virus (HIV) infection. A cohort of 25 HIV patients with progressive multifocal leukoencephalopathy (PML) treated with HAART experienced a median survival of >46 weeks. This is an improvement in prognosis compared with recent historic experience and correlated with HIV RNA viral load reductions. We conclude that current HIV therapy is important in improving the outlook of PML in the setting of HIV. 相似文献
5.
JM Langley JC LeBlanc EE Wang BJ Law NE MacDonald I Mitchell D Stephens J McDonald FD Boucher S Dobson 《Pediatrics》1997,100(6):943-946
OBJECTIVE: To determine nosocomial transmission of respiratory syncytial virus (RSV) in Canadian pediatric hospitals, outcomes associated with nosocomial disease, and infection control practices. DESIGN: A prospective cohort study in the 1992 to 1994 winter respiratory seasons. SETTING: Nine Canadian pediatric university-affiliated hospitals. PARTICIPANTS: Hospitalized children with symptoms of lower respiratory tract infection (at least one of cough, wheezing, dyspnea, tachypnea, and apnea) and RSV antigen identified in a nasopharyngeal aspirate. RESULTS: Of 1516 children, 91 (6%) had nosocomial RSV (NRSV), defined as symptoms of lower respiratory tract infection and RSV antigen beginning >72 hours after admission. The nosocomial ratio (NRSV/[com-munity-acquired RSV {CARSV})] + NRSV) varied by site from 2.8% to 13%. The median length of stay attributable to RSV for community-acquired illness was 5 days, but 10 days for nosocomial illness. Four children with NRSV (4. 4%) died within 2 weeks of infection, compared with 6 (0.42%) with CARSV (relative risk = 10.4, 95% confidence interval: 3.0, 36.4). All sites isolated RSV-positive patients in single rooms or cohorted them. In a multivariate model, no particular isolation policy was associated with decreased nosocomial ratio, but gowning to enter the room was associated with increased risk of RSV transmission (incidence rate ratio 2.81; confidence interval: 1.65, 4.77). CONCLUSIONS: RSV transmission risk in Canadian pediatric hospitals is generally low. Although use of barrier methods varies, all sites cohort or isolate RSV-positive patients in single rooms. Children with risk factors for severe disease who acquire infection nosocomially have prolonged stays and excess mortality. 相似文献
6.
Daniela G Beghini Maria Alice da Cruz-H?fling Priscila Randazzo-Moura Léa Rodrigues-Simioni José Camilo Novello Stephen Hyslop Sérgio Marangoni 《Toxicon》2005,46(6):604-611
We have previously demonstrated that rabbit antisera raised against crotoxin from Crotalus durissus cascavella venom (cdc-crotoxin) and its PLA2 (cdc-PLA2) neutralized the neurotoxicity of this venom and its crotoxin. In this study, we examined the ability of these antisera to neutralize the neurotoxicity of Crotalus durissus terrificus and Bothrops jararacussu venoms and their major toxins, cdt-crotoxin and bothropstoxin-I (BthTX-I), respectively, in mouse isolated phrenic nerve-diaphragm preparations. Immunoblotting showed that antiserum to cdc-crotoxin recognized cdt-crotoxin and BthTX-I, while antiserum to cdc-PLA2 recognized cdt-PLA2 and BthTX-I. ELISA corroborated this cross-reactivity. Antiserum to cdc-crotoxin prevented the neuromuscular blockade caused by C. d. terrificus venom and its crotoxin at a venom/crotoxin:antiserum ratio of 1:3. Antiserum to cdc-PLA2 also neutralized the neuromuscular blockade caused by C. d. terrificus venom or its crotoxin at venom or toxin:antiserum ratios of 1:3 and 1:1, respectively. The neuromuscular blockade caused by B. jararacussu venom and BthTX-I was also neutralized by the antisera to cdc-crotoxin and cdc-PLA2 at a venom/toxin:antiserum ratio of 1:10 for both. Commercial equine antivenom raised against C. d. terrificus venom was effective in preventing the neuromuscular blockade typical of B. jararacussu venom (venom:antivenom ratio of 1:2), whereas for BthTX-I the ratio was 1:10. These results show that antiserum produced against PLA2, the major toxin in C. durissus cascavella venom, efficiently neutralized the neurotoxicity of C. d. terrificus and B. jararacussu venoms and their PLA2 toxins. 相似文献
7.
Cháriston André Dal Belo Gildo Bernardo Leite Marcos Hikari Toyama Sergio Marangoni Alexandre Pinto Corrado Marcos Dias Fontana Andy Southan Edward G Rowan Stephen Hyslop Léa Rodrigues-Simioni 《Toxicon》2005,46(7):736-750
We have isolated a new phospholipase A2 (MiDCA1) from the venom of the coral snake Micrurus dumerilii carinicauda. This toxin, which had a molecular mass of 15,552Da, shared high sequence homology with the PLA2 toxins MICNI A and B from Micrurus nigrocinctus venom (77.7% and 73.1%, respectively). In chick biventer cervicis preparations, MiDCA1 produced concentration- and time-dependent neuromuscular blockade that reached 100% after 120 min (2.4 microM, n = 6); contractures to exogenously applied carbachol (8 microM) and KCl (13 mM) were still seen after complete blockade. In mouse phrenic-nerve diaphragm preparations, MiDCA1 (2.4 microM; n = 6) caused triphasic changes followed by partial neuromuscular blockade. Intracellular recordings of end-plate potentials (EPPs) and miniature end-plate potentials (MEPPs) from mouse diaphragm preparations showed that MiDCA1 increased the quantal content by 386+/-12% after 10 min (n = 14; p<0.05) and caused a triphasic change in the frequency of MEPPs. MiDCA1 also decreased the resting membrane potential, an effect that was prevented by tetrodotoxin and/or low extracellular calcium, but not by d-tubocurarine. The toxin increased the amplitude of mouse sciatic-nerve compound action potentials by 30+/-9% (0.6 microM; p<0.05). Potassium currents elicited in freshly dissociated dorsal root ganglia neurones were blocked by 31+/-1% (n = 4; p<0.05) in the presence of 2.4 microM MiDCA1. These results show that MiDCA1 is a new presynaptic phospholipase A2 that produces neuromuscular blockade in vertebrate nerve-muscle preparations. The triphasic effects seen in mammalian preparations and the facilitatory response were probably caused mainly by the activation of sodium channels, complemented by the blockade of nerve terminal potassium channels. The inability of d-turocurarine to prevent the depolarization by MiDCA1 indicated that cholinergic nicotinic receptors were not involved in this phenomenon. 相似文献
8.
9.
HABIB BOUKERCHE MARIE-HéLèNE RUCHAUD-SPARAGANO CHRISTINE R OUEN JEAN BROCH IER CéCILE KAPLAN & JOHN LOUIS MCGREGOR 《British journal of haematology》1996,92(2):442-451
P-selectin (also called CD62, GMP-140, PADGEM, CD62P) is a recently described member of a family of vascular adhesion receptors expressed by activated platelets and endothelial cells that are involved in leucocyte cell adhesion. The aim of this study was to characterize a new monoclonal antibody (LYP7) directed against activated human blood platelets that inhibits ristocetin-induced platelet aggregation. Immunoadsorbent affinity chromatography and immunoprecipitation studies showed that LYP7 (IgG1) bound a surface-labelled glycoprotein (GP) which changed its apparent molecular mass (Mr) on reduction from 138 kD (situated below GPIIb) to 148 kD (above GPIIbα). LYP7 and S12, a monoclonal antibody directed against P-selectin immunoprecipitated the same band. Using ELISA assay, purified P-selectin was shown to bind LYP7 and S12 monoclonal antibodies. Binding sites of 125I-labelled LYP7, which was greatly increased on thrombin-stimulated (2 U/ml) washed platelets (10825±2886, mean ±SD) (Kd=1.5±0.5 nm ) compared to resting platelets (2801±1278, mean ±SD) (Kd=1.5±0.6 nm ), was found to be normal on thrombin-stimulated platelets taken from a patient with grey platelet syndrome or a patient with Glanzmann thrombasthenia. LYP7 (IgG1, F(ab′)2 or Fab fragments) inhibited ristocetin-induced platelet aggregation of platelets in a dose-dependent fashion without affecting the binding of von Willebrand (vWf ) factor. However, agglutination of formaldehyde-fixed platelets induced by ristocetin was not affected by monoclonal antibody LYP7. In addition, the binding of thrombin-activated platelets to neutrophils was inhibited by monoclonal antibody LYP7. These results strongly suggest that P-selectin, by promoting cell–cell contact, may play an active role in platelet–platelet interactions. 相似文献
10.
Plesner T; Ploug M; Ellis V; Ronne E; Hoyer-Hansen G; Wittrup M; Pedersen TL; Tscherning T; Dano K; Hansen NE 《Blood》1994,83(3):808-815
The cellular receptor for urokinase-type plasminogen activator (uPAR) binds pro-urokinase (pro-uPA) and facilitates its conversion to enzymatically active urokinase (uPA). uPA in turn activates surface- bound plasminogen to plasmin, a process of presumed importance for a number of biologic processes including cell migration and resolution of thrombi. We have previously shown that uPAR is expressed on the plasma membrane of circulating neutrophils, and we now report that stimulation with phorbol myristate acetate (PMA), FMLP, or tumor necrosis factor- alpha results in a rapid increase in the expression of uPAR. This process is accompanied by an increased cell-associated plasminogen activation after preincubation of neutrophils with pro-uPA in vitro. By subcellular fractionation of unstimulated neutrophils, 50% of uPAR is recovered in fractions containing latent alkaline phosphatase, corresponding to an intracellular compartment of easily mobilizable secretory vesicles distinct from both primary and specific granules, whereas the remaining 50% of uPAR is associated with a compartment eluting close to the specific granules. In contrast, the ligand pro-uPA is primarily (approximately 80%) found in the specific granules, but small amounts of pro-uPA/uPA (approximately 20%) coelute with latent alkaline phosphatase. Stimulation of neutrophils with FMLP results in translocation of uPAR as well as of pro-uPA from the secretory vesicles, whereas stimulation with PMA is required to translocate material from specific granules. Flow cytometry of neutrophils saturated with exogenous diisopropyl fluorophosphate-uPA shows a large excess (approximately 90%) of unoccupied uPAR on resting as well as FMLP- and PMA-stimulated neutrophils, suggesting a possible role for exogenous pro-uPA in providing neutrophils with a potential for plasminogen activation. These processes may be important for neutrophil extravasation and migration through extracellular matrix and for the contribution of neutrophils to resolution of thrombi. 相似文献