全文获取类型
收费全文 | 378篇 |
免费 | 29篇 |
国内免费 | 17篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 34篇 |
妇产科学 | 3篇 |
基础医学 | 43篇 |
口腔科学 | 11篇 |
临床医学 | 48篇 |
内科学 | 98篇 |
皮肤病学 | 7篇 |
神经病学 | 34篇 |
特种医学 | 48篇 |
外科学 | 27篇 |
综合类 | 9篇 |
预防医学 | 13篇 |
眼科学 | 4篇 |
药学 | 13篇 |
中国医学 | 1篇 |
肿瘤学 | 29篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2021年 | 5篇 |
2020年 | 6篇 |
2019年 | 8篇 |
2018年 | 7篇 |
2017年 | 7篇 |
2016年 | 6篇 |
2015年 | 11篇 |
2014年 | 8篇 |
2013年 | 15篇 |
2012年 | 8篇 |
2011年 | 12篇 |
2010年 | 22篇 |
2009年 | 26篇 |
2008年 | 5篇 |
2007年 | 19篇 |
2006年 | 12篇 |
2005年 | 6篇 |
2004年 | 15篇 |
2003年 | 3篇 |
2002年 | 8篇 |
2001年 | 6篇 |
2000年 | 8篇 |
1999年 | 5篇 |
1998年 | 28篇 |
1997年 | 26篇 |
1996年 | 20篇 |
1995年 | 14篇 |
1994年 | 17篇 |
1993年 | 6篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1989年 | 6篇 |
1988年 | 11篇 |
1987年 | 8篇 |
1986年 | 9篇 |
1985年 | 9篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 10篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1926年 | 1篇 |
排序方式: 共有424条查询结果,搜索用时 15 毫秒
91.
CP Murray PM Wong J Louw GW Waterer 《Journal of Medical Imaging and Radiation Oncology》2009,53(4):339-344
To determine the prevalence of small lung nodules on low‐dose helical computed tomography (CT) in a Western Australian cohort of asymptomatic long‐term cigarette smokers and to compare this with a large, similarly derived cohort of North Americans from the Mayo Clinic Lung Cancer Screening Trial. Forty‐nine asymptomatic long‐term cigarette smokers of minimum age 50 years underwent a low‐dose 64‐slice helical CT of the lungs. Images were viewed on a soft copy reporting station with thin section axial and coronal images, maximum intensity projection images, and advanced image manipulation tools. The prevalence of all nodules was 39%, significantly lower than the Mayo Clinic cohort prevalence of 51% (P < 0.01, Fisher's exact test), despite the use of more advanced imaging technology and image manipulation designed to increase the sensitivity for nodules. The prevalence of small nodules in asymptomatic long‐term cigarette smokers in Western Australia is high, though significantly less than that found in a large study in North America. The authors postulate this is due to the relatively low rates of mycobacterium tuberculosis and soil‐derived fungal pulmonary infections in Western Australia, as well as a lower degree of urban air pollution. 相似文献
92.
Characterization of a gene encoding survival motor neuron (SMN)-related protein, a constituent of the spliceosome complex 总被引:2,自引:3,他引:2
Talbot K; Miguel-Aliaga I; Mohaghegh P; Ponting CP; Davies KE 《Human molecular genetics》1998,7(13):2149-2156
Mutations in the gene encoding the Survival Motor Neuron (SMN) protein are
responsible for autosomal recessive proximal spinal muscular atrophy (SMA).
SMN orthologues have been identified in the nematode worm Caenorhabditis
elegans and the yeast Schizosaccharomyces pombe but, to date, no human
paralogues have been described. Here we describe identification and
characterization of an SMN-related protein (SMNrp) gene that encodes a
novel protein of 239 amino acids, which has recently been identified as a
constituent of the spliceosome complex and designated SPF30. Significant
similarity to the SMN protein is apparent only within a central region of
SMNrp that represents a tudor domain. The SMNrp/SPF30 gene has been mapped
to chromosome 10q23. It is differentially expressed, with abundant levels
in skeletal muscle. An exclusively nuclear localization for SMNrp in
cultured cells and muscle sections was revealed using GFP fusion constructs
and thereafter confirmed with a polyclonal antibody raised against SMNrp.
Overexpression of SMNrp as a fusion protein in HeLa cells in culture
induced dose-dependent apoptosis with positive TUNEL staining. In addition
to a possible role for this protein as a pro-apoptotic factor, SMN and its
related protein share significant similarities in sequence and cellular
function.
相似文献
93.
IMPT1, an imprinted gene similar to polyspecific transporter and multi- drug resistance genes 总被引:5,自引:1,他引:5
Dao D; Frank D; Qian N; O'Keefe D; Vosatka RJ; Walsh CP; Tycko B 《Human molecular genetics》1998,7(4):597-608
Human chromosome 11p15.5 and distal mouse chromosome 7 include a
megabase-scale chromosomal domain with multiple genes subject to parental
imprinting. Here we describe mouse and human versions of a novel imprinted
gene, IMPT1 , which lies between IPL and p57 KIP2 and which encodes a
predicted multi-membrane-spanning protein similar to bacterial and
eukaryotic polyspecific metabolite transporter and multi- drug resistance
pumps. Mouse Impt1 and human IMPT1 mRNAs are highly expressed in tissues
with metabolite transport functions, including liver, kidney, intestine,
extra-embryonic membranes and placenta, and there is strongly preferential
expression of the maternal allele in various mouse tissues at fetal stages.
In post-natal tissues there is persistent expression, but the allelic bias
attenuates. An allelic expression bias is also observed in human fetal and
post-natal tissues, but there is significant interindividual variation and
rare somatic allele switching. The fact that Impt1 is relatively repressed
on the paternal allele, together with data from other imprinted genes,
allows a statistical conclusion that the primary effect of human chromosome
11p15.5/mouse distal chromosome 7 imprinting is domain-wide relative
repression of genes on the paternal homolog. Dosage regulation of the
metabolite transporter gene(s) by imprinting might regulate placental and
fetal growth.
相似文献
94.
Development of hatching blastocysts from immature human oocytes following in-vitro maturation and fertilization using a co-culture system 总被引:8,自引:0,他引:8
Hwu YM; Lee RK; Chen CP; Su JT; Chen YW; Lin SP 《Human reproduction (Oxford, England)》1998,13(7):1916-1921
Recently, in-vitro maturation (IVM) of immature human oocytes recovered
from non-stimulated follicles has been applied in the treatment of
infertility. However, in previous reports, very few embryos cultured in
conventional medium have reached the expanded blastocyst stage following
in-vitro maturation and fertilization (IVM/IVF). The objective of this
study was to investigate whether the developmental competence of human
embryos following IVM/IVF could be enhanced by the use of a human ampullary
cell co-culture system. Immature human oocytes were aspirated from small
follicles at Caesarean section and then cultured in medium containing human
menopausal gonadotrophin for 36 to 48 h, followed by insemination. Zygotes
were randomly cultured either in conventional culture medium alone or in
the co-culture system. Of 48 embryos cultured in conventional medium alone,
all arrested at the 2-16- cell stage on day 3 after insemination. Of 46
embryos cultured in the co-culture system, 26 embryos (56.5%) arrested at
the 2-16-cell stage. Six embryos (13%) developed to the morula stage.
Fourteen embryos (30.4%) developed to expanded blastocysts and two
blastocysts were hatching on day 7 after insemination. We conclude that
co-culture significantly enhances the development of blastocysts in embryos
resulting from IVM/IVF.
相似文献
95.
D Siassakos JF Crofts C Winter CP Weiner TJ Draycott 《BJOG : an international journal of obstetrics and gynaecology》2009,116(8):1028-1032
Confidential enquiries into poor perinatal outcomes have identified deficiencies in team working as a common factor and have recommended team training in the management of obstetric emergencies. Isolated aviation-based team training programmes have not been associated with improved perinatal outcomes when applied to labour ward settings, whereas obstetric-specific training interventions with integrated teamwork have been associated with clinical improvements. This commentary reviews obstetric emergency training programmes from hospitals that have demonstrated improved outcomes to determine the active components of effective training. The common features identified were: institution-level incentives to train; multi-professional training of all staff in their units; teamwork training integrated with clinical teaching and use of high fidelity simulation models. Local training also appeared to facilitate self-directed infrastructural change. 相似文献
96.
Specificity of autoantibodies in autoimmune thrombocytopenia 总被引:12,自引:5,他引:12
In 42 patients with autoimmune thrombocytopenia (AITP) and a positive direct platelet suspension immunofluorescence test (PSIFT), the antigenic specificity of the autoantibodies was studied. Because the autoantibodies were often not detectable in the serum and additional HLA antibodies may disturb the reaction pattern with the platelet panel, we used eluates prepared from the patients' platelets for this study. Thirty-five patients had antibodies equally reactive with normal platelets, irrespective of their antigenic make-up, but not with the platelets from two Glanzmann's disease patients. Absorption and elution experiments in two patients showed that his was probably not due to the presence of a combination of anti-Zwa and anti-Zwb antibodies. Thus, the majority of autoantibodies against platelets seems to be directed against antigenic determinants not present on Glanzmann's disease platelets, but perhaps located on the platelet-membrane glycoproteins IIb and/or IIIa. In ten patients, antibodies of no, or still unknown, specificity were detected. Three of these had additional antibodies not reactive with the platelets of the two Glanzmann patients. 相似文献
97.
Warkentin TE; Hayward CP; Boshkov LK; Santos AV; Sheppard JA; Bode AP; Kelton JG 《Blood》1994,84(11):3691-3699
Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia. 相似文献
98.
Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis 总被引:85,自引:19,他引:85
Koopman G; Reutelingsperger CP; Kuijten GA; Keehnen RM; Pals ST; van Oers MH 《Blood》1994,84(5):1415-1420
Apoptosis, or programmed cell death, is a general mechanism for removal of unwanted cells from the immune system. It is characterized by chromatin condensation, a reduction in cell volume, and endonuclease cleavage of DNA into oligonucleosomal length fragments. Apoptosis is also accompanied by a loss of membrane phospholipid asymmetry, resulting in the exposure of phosphatidylserine at the surface of the cell. Expression of phosphatidylserine at the cell surface plays an important role in the recognition and removal of apoptotic cells by macrophages. Here we describe a new method for the detection of apoptotic cells by flow cytometry, using the binding of fluorescein isothiocyanate-labeled annexin V to phosphatidylserine. When Burkitt lymphoma cell lines and freshly isolated germinal center B cells are cultured under apoptosis inducing conditions, all cells showing chromatin condensation strongly stain with annexin V, whereas normal cells are annexin V negative. Moreover, DNA fragmentation is only found in the annexin V-positive cells. The nonvital dye ethidium bromide was found to stain a subpopulation of the annexin V-positive apoptotic cells, increasing with time. Our results indicate that the phase in apoptosis that is characterized by chromatin condensation coincides with phosphatidylserine exposure. Importantly, it precedes membrane damage that might lead to release from the cells of enzymes that are harmful to the surrounding tissues. Annexin V may prove important in further unravelling the regulation of apoptosis. 相似文献
99.
Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4 总被引:6,自引:3,他引:6
Heparin-induced thrombocytopenia (HIT) is an important complication of heparin therapy. Although there is general agreement that platelet activation in vitro by the HIT IgG is mediated by the platelet Fc receptor, the interaction among the antibody, heparin, and platelet membrane components is uncertain and debated. In this report, we describe studies designed to address these interactions. We found, as others have noted, that a variety of other sulfated polysaccharides could substitute for heparin in the reaction. Using polysaccharides selected for both size and charge, we found that reactivity depended on two independent factors: a certain minimum degree of sulfation per saccharide unit and a certain minimum size. Hence, highly sulfated but small (< 1,000 daltons) polysaccharides were not reactive nor were large but poorly sulfated polysaccharides. The ability of HIT IgG to recognize heparin by itself was tested by Ouchterlony gel diffusion, ammonium sulfate and polyethylene glycol precipitation, and equilibrium dialysis. No technique demonstrated reactivity. However, when platelet releasate was added to heparin and HIT IgG, a 50-fold increase in binding of radio-labeled heparin to HIT IgG was observed. The releasate was then depleted of proteins capable of binding to heparin by immunoaffinity chromatography. Only platelet factor 4-immunodepleted releasate lost its reactivity with HIT IgG and heparin. Finally, to determine whether the reaction occurred on the surface of platelets or in the fluid phase, washed platelets were incubated with HIT IgG or heparin and after a wash step, heparin or HIT IgG was added, respectively. Reactivity was only noted when platelets were preincubated with heparin. Consistent with these observations was the demonstration of the presence of PF4 on platelets using flow cytometry. These studies indicate that heparin and other large, highly sulfated polysaccharides bind to PF4 to form a reactive antigen on the platelet surface. HIT IgG then binds to this complex with activation of platelets through the platelet Fc receptors. 相似文献
100.
C Pothoulakis U Galili I Castagliuolo CP Kelly S Nikulasson PK Dudeja TA Brasitus JT LaMont 《Gastroenterology》1996,110(6):1704-1712
BACKGROUND & AIMS: Nearly all human sera contain an immunoglobulin G antibody (antigalactose) that binds the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc expressed on cells from most mammals but not humans. Because the Clostridium difficile toxin A receptor in rodents contains this trisaccharide, the aim of this study was to examine whether antigalactose could mimic the enterotoxic effects of toxin A and bind to receptors containing this trisaccharide. METHODS: Fluid secretion, [3H]-mannitol permeability, and release of rat mast cell protease II and prostaglandin E2 were measured after luminal exposure of rat colon to either purified human anti-galactose, control immunoglobulin G, toxin A, or buffer. RESULTS: Toxin A (5 micrograms) and antigalactose (250 micrograms) but not control immunoglobulin (250 micrograms) stimulated colonic fluid secretion and caused increased mannitol permeability and rat mast cell protease II release. Antigalactose and toxin A and, to a lesser degree, control immunoglobulin G also stimulated release of prostaglandin E2, but only toxin A produced acute inflammation of rat colonic mucosa. Antigalactose and toxin A bound specifically to a single class of colonic brush border receptors with dissociation constants of 10(-6) mol/L and 5.4 x 10(-8) mol/L, respectively. CONCLUSIONS: Fluid secretion, increased permeability, and mast cell activation occur in rat colon when toxin A or human antigalactose immunoglobulin G bind to receptors bearing the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc. (Gastroenterology 1996 Jun;110(6):1704-12) 相似文献