全文获取类型
收费全文 | 182篇 |
免费 | 8篇 |
国内免费 | 18篇 |
专业分类
儿科学 | 11篇 |
基础医学 | 31篇 |
临床医学 | 23篇 |
内科学 | 31篇 |
神经病学 | 5篇 |
特种医学 | 39篇 |
外科学 | 8篇 |
综合类 | 12篇 |
预防医学 | 6篇 |
药学 | 23篇 |
肿瘤学 | 19篇 |
出版年
2022年 | 1篇 |
2021年 | 1篇 |
2020年 | 1篇 |
2018年 | 1篇 |
2016年 | 1篇 |
2015年 | 5篇 |
2014年 | 4篇 |
2013年 | 6篇 |
2012年 | 3篇 |
2011年 | 6篇 |
2010年 | 7篇 |
2009年 | 9篇 |
2008年 | 11篇 |
2007年 | 16篇 |
2006年 | 8篇 |
2005年 | 7篇 |
2004年 | 4篇 |
2003年 | 8篇 |
2002年 | 2篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 2篇 |
1998年 | 11篇 |
1997年 | 8篇 |
1996年 | 13篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 7篇 |
1988年 | 9篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 4篇 |
排序方式: 共有208条查询结果,搜索用时 15 毫秒
1.
Mulkerrin EC; Clark BA; Epstein FH 《QJM : monthly journal of the Association of Physicians》1997,90(6):411-415
We studied blood pressure and natriuretic responses to acute salt loading,
and the effect of non-steroidal anti-inflammatory agents on these
responses, in five healthy normotensive women aged 65 to 71 years. Five
women aged 25 to 31 years acted as controls. Intravenous saline loading,
with and without prior ingestion of ibuprofen, was 15 ml/kg/h for 3 h.
Baseline blood pressures were higher in the elderly. Saline infusion
without ibuprofen raised systolic blood pressure (SBP) by about 25 mmHg in
the older group only. Ibuprofen increased baseline SBP in the elderly (129
+/- 6 vs. 116 +/- 5 mmHg, p < 0.05). Saline loading after ibuprofen
again raised blood pressure by about 25 mmHg in the elderly only. The
elderly group showed markedly increased sodium excretion during saline
loading, but this was reduced by ibuprofen. Ibuprofen had no effect on SBP
or sodium excretion in controls. Ageing appears to increase susceptibility
to salt retention and hypertension from non-steroidal anti-inflammatory
agents.
相似文献
2.
Acute thoracic aortic dissection has a high mortality if untreated, so the diagnosis must be rapidly made if mortality is to be lowered significantly. Multiple imaging techniques are often used. This retrospective study from 1988 to 1993 assesses the usefulness in diagnosis of chest X-rays, computed tomography (CT) scanning, aortography, magnetic resonance imaging (MRI), trans-thoracic (TTE) and trans-oesophageal (TOE) echocardiography. Forty-two patients with a final clinical diagnosis of dissection were studied. The diagnosis was confirmed in 16 (13 at surgery and three at autopsy). Three died with dissection given as the only cause for death. Chest X-ray abnormalities were seen in all 19 patients with surgery or death from dissection, with a widened mediastinum and/or dilated aorta being present in 17. In the group of 16 patients with surgery or autopsy proof, CT scans found dissections in 9 of 12 patients studied and correctly classified the type in only five. Aortography was performed in five, with accurate depiction of dissection and type in all. TTE found dissections in three of eight patients imaged by this method. MRI and TOE were performed each on two patients, with accurate depiction of dissection and type in each. Because of the relatively low sensitivity of CT scanning in defining aortic dissections Westmead Hospital is currently assessing the use of TOE as the prime imaging modality prior to surgical intervention. 相似文献
3.
Castillo S Reyes G Tejedor D Mozas P Suarez Y Lasuncion MA Cenarro A Civeira F Alonso R Mata P Pocovi M;Spanish Group of FH 《Human mutation》2002,20(6):477
Familial hypercholesterolemia is a genetic disorder caused by mutations in the LDL receptor gene. During a survey of mutations of LDL receptor gene in Spanish FH patients we found two mutations in the same allele: a missense N543H mutation in exon 11 and a 9bp inframe deletion (2393del9) located in exon 17. This double mutant allele was founded in 10 out of 458 unrelated patients: one homozygous FH [N543H+2393del9] + [N543H+2393del9], one compound heterozygote [N543H+2393del9] + [W-18X+E256K] and 8 heterozygotes. Flow cytometric analysis showed a defective LDL binding (20% of normal value) and internalization (23%) in lymphocytes from the homozygous patient; furthermore, studies of mitogen-stimulated lymphocytes demonstrated that the ability of LDL to support cell proliferation was impaired. Unexpectedly, not all carriers of the double mutant allele develop hypercholesterolemia and, furthermore, cholesterol-lowering treatment of the homozygous patient resulted in a 58% LDL cholesterol reduction. In conclusion, the phenotypic expression in the homozygous and heterozygous patients presented here, as well as the LDL-receptor residual activity, allowed the classification of this mutation as mild extending the group of mild mutations found at homozygosity. 相似文献
4.
Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP) 总被引:8,自引:0,他引:8
Rowe PS; Oudet CL; Francis F; Sinding C; Pannetier S; Econs MJ; Strom TM; Meitinger T; Garabedian M; David A; Macher MA; Questiaux E; Popowska E; Pronicka E; Read AP; Mokrzycki A; Glorieux FH; Drezner MK; Hanauer A; Lehrach H; Goulding JN; O'Riordan JL 《Human molecular genetics》1997,6(4):539-549
Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with
homologies to endopeptidases, on the X-chromosome), are responsible for
X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family
of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has
raised important questions regarding PEX function at the molecular level.
The aim of this study was to analyse 99 HYP families for PEX gene
mutations, and to correlate predicted changes in the protein structure with
Zn2+ metallopeptidase gene function. Primers flanking 22 characterised
exons were used to amplify DNA by PCR, and SSCP was then used to screen for
mutations. Deletions, insertions, nonsense mutations, stop codons and
splice mutations occurred in 83% of families screened for in all 22 exons,
and 51% of a separate set of families screened in 17 PEX gene exons.
Missense mutations in four regions of the gene were informative regarding
function, with one mutation in the Zn2+-binding site predicted to alter
substrate enzyme interaction and catalysis. Computer analysis of the
remaining mutations predicted changes in secondary structure,
N-glycosylation, protein phosphorylation and catalytic site molecular
structure. The wide range of mutations that align with regions required for
protease activity in NEP suggests that PEX also functions as a protease,
and may act by processing factor(s) involved in bone mineral metabolism.
相似文献
5.
单克隆抗体—表阿霉素免疫偶合物的制备和体外活性 总被引:14,自引:0,他引:14
用双功能试剂己二酰肼制备腙键连接的聚谷氨酸—表阿霉素,通过控制交联条件,所得产物克服了大分子自身交联的缺点,交联率较高。聚谷氨酸的载药量与分子量呈正比,平均每8~11个谷氨酸单体连接1分子表阿霉素。分子量为14300的聚谷氨酸做载体其载药量为1:11,与单抗交联所得的偶合物McAb:PGA:PAR为1:2:22。偶合物较好地保留了抗体活性,体外细胞毒性较游离药物略有下降,但表现出单抗介导的靶细胞选择性杀伤作用。本研究用腙键交联法成功地制备了药/抗比高且体外有效的免疫偶合物,为进一步制备细胞靶向的肿瘤化疗制剂奠定了基础。 相似文献
6.
7.
Clinicopathological analysis of papillary thyroid cancer with PIK3CA alterations in a Middle Eastern population 总被引:1,自引:0,他引:1
Abubaker J Jehan Z Bavi P Sultana M Al-Harbi S Ibrahim M Al-Nuaim A Ahmed M Amin T Al-Fehaily M Al-Sanea O Al-Dayel F Uddin S Al-Kuraya KS 《The Journal of clinical endocrinology and metabolism》2008,93(2):611-618
CONTEXT: Genetic aberration in phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been detected in numerous and diverse human cancers. PIK3CA, which encodes for the catalytic subunit of p110alpha of PI3K, is amplified in some cases of papillary thyroid cancer (PTC). Mutations in the PIK3CA have also been identified in thyroid cancers and, although relatively common in anaplastic thyroid carcinoma, are uncommon in PTC. OBJECTIVE: The objective of the study was to investigate genetic alterations like PIK3CA gene mutation, PIK3CA amplification, RAS, and RAF mutations and to further explore the relationship of these genetic alterations with various clinicopathological characteristics in Middle Eastern PTC. DESIGN: We used the fluorescence in situ hybridization technique for analysis of PIK3CA amplification from 536 PTC cases, and selected amplified samples were further validated by real-time quantitative PCR. Mutation analysis was done by direct DNA sequencing of PIK3CA, N2-RAS, and BRAF genes. RESULTS: PIK3CA amplification was seen in 265 of 499 PTC cases analyzed (53.1%); PIK3CA gene mutations in four of 207 PTC (1.9%); N2-RAS mutations in 16 of 265 PTC (6%); and BRAF mutations in 153 of 296 PTC (51.7%). N-RAS mutations were-associated with an early stage (P = 0.0465) and lower incidence of extrathyroidal extension (P = 0.027), whereas BRAF mutations were-associated with metastasis (P = 0.0274) and poor disease-free survival (P = 0.0121) in PTCs. CONCLUSION: A higher incidence of PIK3CA alterations and the possible synergistic effect of PIK3CA alterations and BRAF mutations suggest their major role in Middle Eastern PTC tumorigenesis and argue for therapeutic targeting of PI3K/AKT and MAPK pathways. 相似文献
8.
Erythropoietin production in a primary culture of human renal carcinoma cells maintained in nude mice 总被引:4,自引:1,他引:4
The present studies report erythropoietin (Ep) production in primary cultures of a human renal carcinoma from a patient with erythrocytosis that has been serially transplanted to BALB/c nude mice. The levels of erythropoietin in the culture media were estimated using the exhypoxic polycythemic mouse assay (EHPCMA), fetal mouse liver erythroid colony- forming technique (FMLC), and a radioimmunoassay (RIA). The spent culture media of the exponentially growing cells contained less than 10 mU/ml of Ep measured by RIA. However, after the cells became confluent, Ep levels (RIA) in the spent media showed a marked increase to approximately 300 mU/ml. Ep levels estimated using the FMLC and EHPCMA were approximately 2/3 and 1/10, respectively, of those measured by RIA. Rabbit antiserum to highly purified human urinary Ep (70,400 U/mg protein) was utilized for immunocytochemical (peroxidase-antiperoxidase method) localization of Ep in the cultured cells. Very few of the cells in exponential growth exhibited Ep-like immunoreactivity, whereas intense Ep-like immunoreactivity was observed in the cytoplasm of the cells maintained in culture for a prolonged period after reaching confluency. The most intense staining was observed in some of the cells forming domes. The domes developed after the cells reached confluency, and their numbers increased with increasing time in confluent culture, in parallel with the increase in Ep levels in the spent media. This primary cell culture system of a renal cell carcinoma maintained in nude mice, which produces immunologically and biologically active Ep, may provide a useful model for studies of the mechanism of Ep production. 相似文献
9.
Uddin S Hussain AR Ahmed M Siddiqui K Al-Dayel F Bavi P Al-Kuraya KS 《Haematologica》2012,97(7):1092-1100
Background
FoxM1 has been shown to play a critical role in the pathogenesis of various epithelial malignancies. However, its role in lymphoid malignancies has not been fully clarified. We, therefore, investigated the role of FoxM1 expression in a large cohort of diffuse large B-cell lymphoma samples and panel of cell lines.Design and Methods
FoxM1 expression was investigated in a large series of diffuse large B-cell lymphoma tissues in a tissue microarray format by immunohistochemistry. Apoptosis was measured by flow cytometry and protein expression was detected by immunoblotting using diffuse large B-cell lymphoma cell lines following treatment with either pharmacological inhibitor of FoxM1 or small interference RNA knockdown strategy. Invasion/migration and soft agar colony assays were also performed following treatment with FoxM1 inhibitor.Results
FoxM1 expression was detected in 84.6% of diffuse large B-cell lymphoma tumors and found to be significantly associated with proliferative tumor marker Ki67 (P<0.0001), matrix metalloproteinases-2 (P=0.0008), matrix metalloproteinases-9 (P=0.0002), S-phase kinase associated protein-2 (P<0.0001) and inversely associated with p27 expression (P=0.0215). Expression of small interference RNA targeted against FoxM1 or treatment of diffuse large B-cell lymphoma cells with thiostrepton caused its downregulation accompanied by decreased expression of matrix metalloproteinases-2 and matrix metalloproteinases-9. Inhibition of FoxM1 in diffuse large B-cell lymphoma cells also decreased invasive and migratory capability, and induced caspase dependent apoptosis via activation of the mitochondrial apoptotic pathway. Finally, combined thiostrepton and bortezomib at sub-toxic doses led to efficient apoptosis in diffuse large B-cell lymphoma cells.Conclusions
Altogether, these results suggest that FoxM1 is over-expressed in the majority of diffuse large B-cell lymphoma samples. These data also indicate that targeting FoxM1 signaling can serve as a potential therapeutic modality in the management of diffuse large B-cell lymphoma. 相似文献10.