全文获取类型
收费全文 | 1165篇 |
免费 | 135篇 |
国内免费 | 8篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 70篇 |
妇产科学 | 10篇 |
基础医学 | 149篇 |
口腔科学 | 60篇 |
临床医学 | 137篇 |
内科学 | 263篇 |
皮肤病学 | 21篇 |
神经病学 | 64篇 |
特种医学 | 165篇 |
外科学 | 87篇 |
综合类 | 67篇 |
预防医学 | 79篇 |
眼科学 | 29篇 |
药学 | 62篇 |
中国医学 | 1篇 |
肿瘤学 | 40篇 |
出版年
2023年 | 6篇 |
2021年 | 10篇 |
2020年 | 10篇 |
2019年 | 17篇 |
2018年 | 23篇 |
2017年 | 9篇 |
2016年 | 29篇 |
2015年 | 33篇 |
2014年 | 40篇 |
2013年 | 54篇 |
2012年 | 46篇 |
2011年 | 28篇 |
2010年 | 48篇 |
2009年 | 54篇 |
2008年 | 34篇 |
2007年 | 45篇 |
2006年 | 39篇 |
2005年 | 42篇 |
2004年 | 22篇 |
2003年 | 30篇 |
2002年 | 25篇 |
2001年 | 28篇 |
2000年 | 25篇 |
1999年 | 18篇 |
1998年 | 42篇 |
1997年 | 49篇 |
1996年 | 47篇 |
1995年 | 42篇 |
1994年 | 30篇 |
1993年 | 37篇 |
1992年 | 18篇 |
1991年 | 16篇 |
1990年 | 13篇 |
1989年 | 27篇 |
1988年 | 24篇 |
1987年 | 16篇 |
1986年 | 21篇 |
1985年 | 16篇 |
1984年 | 13篇 |
1983年 | 21篇 |
1982年 | 12篇 |
1981年 | 20篇 |
1980年 | 17篇 |
1979年 | 13篇 |
1978年 | 21篇 |
1977年 | 17篇 |
1976年 | 15篇 |
1974年 | 8篇 |
1973年 | 5篇 |
1972年 | 6篇 |
排序方式: 共有1308条查询结果,搜索用时 15 毫秒
21.
22.
Red blood cell (RBC) protein 4.2 deficiency is often associated with a moderate nonimmune hemolytic anemia, splenomegaly, and osmotically fragile RBCs resembling, but not identical to, hereditary spherocytosis (HS). In the Japanese type of protein 4.2 deficiency (protein 4.2Nippon), the anemia is associated with a point mutation in the protein 4.2 cDNA. In this report, we describe a patient with moderate and apparently episodic nonimmune hemolytic anemia with splenomegaly, spherocytosis, osmotically fragile RBCs, reduced whole cell deformability, and abnormally dense cells. Sodium dodecyl sulfate- polyacrylamide gel electrophoresis analysis of the proposita's RBC membrane proteins showed an 88% deficiency of protein 4.2 and a 30% deficiency of glyceraldehyde-3-phosphate dehydrogenase (band 6). Structural and molecular analyses of the proposita's protein 4.2 were normal. In contrast, limited tryptic digestion of the proposita's band 3 showed a homozygous abnormality in the cytoplasmic domain. Analysis of the pedigree disclosed six members who were heterozygotes for the band 3 structural abnormality and one member who was a normal homozygote. Direct sequence analysis of the abnormal band 3 tryptic peptide suggested that the structural abnormality resided at or near residue 40. Sequence analysis of the proposita's band 3 cDNA showed a 232G-->A mutation resulting in a 40glutamic acid-->lysine substitution (band 3Montefiore). Allele-specific oligonucleotide hybridization was used to probe for the mutation in the pedigree, showing that the proposita was homozygous, and the pedigree members who were heterozygous for the band 3 structural abnormality were also heterozygous for the band 3Montefiore mutation. The band 3Montefiore mutation was absent in 26 chromosomes from race-matched controls and in one pedigree member who did not express the band 3 structural abnormality. In coincidence with splenectomy, the proposita's anemia was largely corrected along with the disappearance of most spherocytes and considerable improvements of RBC osmotic fragility, whole cell deformability, and cell density. We conclude that this hereditary hemolytic anemia is associated with the homozygous state for band 3Montefiore (40glutamic acid-->lysine) and a decreased RBC membrane content of protein 4.2. We speculate that band 3 structural abnormalities can result in defective interactions with protein 4.2 and band 6, and in particular, that the region of band 3 containing 40glutamic acid is involved directly or indirectly in interactions with these proteins. 相似文献
23.
Monika Oláhová Tobias B Haack Charlotte L Alston Jessica AC Houghton Langping He Andrew AM Morris Garry K Brown Robert McFarland Zofia MA Chrzanowska-Lightowlers Robert N Lightowlers Holger Prokisch Robert W Taylor 《European journal of human genetics : EJHG》2015,23(7):935-939
Isolated mitochondrial complex IV (cytochrome c oxidase) deficiency is an important cause of mitochondrial disease in children and adults. It is genetically heterogeneous, given that both mtDNA-encoded and nuclear-encoded gene products contribute to structural components and assembly factors. Pathogenic variants within these proteins are associated with clinical variability ranging from isolated organ involvement to multisystem disease presentations. Defects in more than 10 complex IV assembly factors have been described including a recent Lebanese founder mutation in PET100 in patients presenting with Leigh syndrome. We report the clinical and molecular investigation of a patient with a fatal, neonatal-onset isolated complex IV deficiency associated with multiorgan involvement born to consanguineous, first-cousin British Asian parents. Exome sequencing revealed a homozygous truncating variant (c.142C>T, p.(Gln48*)) in the PET100 gene that results in a complete loss of enzyme activity and assembly of the holocomplex. Our report confirms PET100 mutation as an important cause of isolated complex IV deficiency outside of the Lebanese population, extending the phenotypic spectrum associated with abnormalities within this gene. 相似文献
24.
Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures 总被引:6,自引:9,他引:6
Lokhorst HM; Lamme T; de Smet M; Klein S; de Weger RA; van Oers R; Bloem AC 《Blood》1994,84(7):2269-2277
Long-term bone marrow cultures (LTBMC) from patients with multiple myeloma (MM) and normal donors were analyzed for immunophenotype and cytokine production. Both LTBMC adherent cells from myeloma and normal donor origin expressed CD10, CD13, the adhesion molecules CD44, CD54, vascular cell adhesion molecule 1, very late antigen 2 (VLA-2), and VLA- 5, and were positive for extracellular matrix components fibronectin, laminin, and collagen types 3 and 4. LTBMC from myeloma patients and normal donors spontaneously secreted interleukin-6 (IL-6). However, levels of IL-6 correlated with the stage of disease; highest levels of IL-6 were found in LTBMC from patients with active myeloma. To identify the origin of IL-6 production, LTBMC from MM patients and normal donors were cocultured with BM-derived myeloma cells and cells from myeloma cell lines. IL-6 was induced by plasma cell lines that adhered to LTBMC such as ARH-77 and RPMI-8226, but not by nonadhering cell lines U266 and FRAVEL. Myeloma cells strongly stimulated IL-6 secretion in cocultures with LTBMC adherent cells from normal donors and myeloma patients. When direct cellular contact between LTBMC and plasma cells was prevented by tissue-culture inserts, no IL-6 production was induced. This implies that intimate cell-cell contact is a prerequisite for IL-6 induction. Binding of purified myeloma cells to LTBMC adherent cells was partly inhibited by monoclonal antibodies against adhesion molecules VLA-4, CD44, and lymphocyte function-associated antigen 1 (LFA-1) present on the plasma cell. Antibodies against VLA-4, CD29, and LFA-1 also inhibited the induced IL-6 secretion in plasma cell-LTBMC cocultures. In situ hybridization studies performed before and after coculture with plasma cells indicated that LTBMC adherent cells produce the IL-6. These results suggest that the high levels of IL-6 found in LTBMC of MM patients with active disease are a reflection of their previous contact with tumor cells in vivo. These results provide a new perspective on tumor growth in MM and emphasize the importance of plasma cell-LTBMC interaction in the pathophysiology of MM. 相似文献
25.
G. Adriana Perez Karen Moomaw Rose Billy A. Caceres Wanda Spurlock Barbara Bowers Barbara Lutz Cynthia Arslanian-Engoren Karin Reuter-Rice Toby Bressler Mona Wicks Diana Taylor Versie Johnson-Mallard Elizabeth Kostas-Polston Teresa Hagan Desiree Bertrand Susan C. Reinhard 《Nursing outlook》2018,66(3):337-340
26.
Transbronchial lung biopsy via the fiberoptic bronchoscope 总被引:6,自引:0,他引:6
27.
BACKGROUND: Chronic systemic inflammation may contribute to accelerated atherosclerosis and increased arterial stiffness in patients with rheumatoid arthritis (RA). In addition to lowering cholesterol, statins have immunomodulatory effects which may be especially beneficial in patients with RA who have systemic immune activation. OBJECTIVE: To investigate the effect of atorvastatin on the augmentation index (AIx: a measure of arterial stiffness) and systemic inflammation in RA. METHODS: 29 patients with RA (mean (SD) age 55 (13) years) with moderately active disease of long duration were studied. AIx, lipid levels, serum inflammatory markers, and disease activity score were measured before and after 12 weeks of atorvastatin 20 mg daily. RESULTS: AIx improved significantly from 34.1 (11.6)% to 29.9 (11)% (p = 0.0002), with the greatest improvements in AIx occurring in those subjects with the highest disease activity scores (r = -0.5, p = 0.007). Total and LDL cholesterol were reduced from 5.5 (0.9) to 3.9 (0.7) mmol/l and 3.3 (0.8) to 1.9 (0.6) mmol/l, respectively (p = 0.0001). Serum inflammatory markers remained unchanged during the study. CONCLUSIONS: Atorvastatin significantly reduced arterial stiffness in patients with RA. The greatest improvements were seen in patients with more active disease, suggesting that, in addition to the beneficial effects of cholesterol reduction, immune modulation may contribute to the cardioprotective effect of statins. 相似文献
28.
Australian mortality statistics for rheumatoid arthritis 1950-81: analysis of death certificate data. 下载免费PDF全文
An analysis of mortality related to rheumatoid arthritis (RA) in Australia for the period 1950 to 1981 was undertaken based on information recorded in death certificates. These data include every death over a 32 year period where RA was considered to be the underlying cause. Death from RA was commonly reported (0.17% of all deaths). The mean age at death from RA in both sexes exceeded that of the general population for most of the period. There was little difference between patients dying of RA and the general population for age at death in the over 50 years' age group. There was a significant decrease in mortality for women dying of RA over the age of 75. RA accounted for more deaths in women than in men (in a ratio of 2.2:1). Men tended to die at a younger age from RA than did women. The impact of RA remained relatively constant in relation both to the total causes of death and to deaths due to other musculoskeletal diseases. There was a significant decline, however, in female RA deaths as a percentage of deaths due to all musculoskeletal diseases. Cohort analysis does not indicate any marked effect from extrinsic factors on mortality due to RA. 相似文献
29.
Use of monoclonal antibodies to detect disease associated HLA-DRB1 alleles and the shared epitope in rheumatoid arthritis 下载免费PDF全文
I. Wicks G. McColl A. D'Amico L. Dougherty B. Tait 《Annals of the rheumatic diseases》1997,56(2):135-139
OBJECTIVE—To use a panel of monoclonal antibodies (Mab) which recognise HLA class II alleles associated with rheumatoid arthritis for fluorescence activated cell sorter (FACS) analysis of peripheral blood mononuclear cells (PBMNC) from patients with early and established rheumatoid arthritis and to compare these results against DNA oligotyping of HLA class II molecules in the same patients.
METHODS—27 patients (18 from an early arthritis clinic, nine with established rheumatoid arthritis) were studied using both techniques. PBMNC were stained with Mab which recognise the shared epitope, the HLA-DRB1*04 molecule and its *0401, *0404 subtypes in the presence of bound peptide. Mab stained cells were analysed by FACS. Genomic DNA was prepared from PBMNC and used for DNA oligotyping and sequencing by standard methods.
RESULTS—FACS analysis of Mab stained PBMNC gave identical results to those obtained by DNA oligotyping in 26/27 patients. The antibodies identified the shared epitope in 14/14 cases and the presence of an HLA-DRB1*04 molecule in 12/12 cases. HLA-DRB1*0404 was identified in 4/4 cases. HLA-DRB1*0401 was identified in 5/6 cases. One patient oligotyped as HLA-DRB1*0401, but consistently failed to react with the *0401 Mab. DNA sequencing of the second exon of the HLA-DRB1*0401 allele in this patient confirmed a normal HLA-DRB1*0401 genotype.
CONCLUSIONS—FACS analysis of PBMNC stained with Mab recognising the shared epitope and rheumatoid arthritis associated HLA susceptibility molecules provides a rapid, reliable, and more accessible alternative to DNA oligotyping. The apparent discordance between phenotypic and genetic analysis of HLA-DRB1*0401 in one patient, may reflect variability in HLA-DRB1*0401 gene expression or in class II peptide presentation.
相似文献
METHODS—27 patients (18 from an early arthritis clinic, nine with established rheumatoid arthritis) were studied using both techniques. PBMNC were stained with Mab which recognise the shared epitope, the HLA-DRB1*04 molecule and its *0401, *0404 subtypes in the presence of bound peptide. Mab stained cells were analysed by FACS. Genomic DNA was prepared from PBMNC and used for DNA oligotyping and sequencing by standard methods.
RESULTS—FACS analysis of Mab stained PBMNC gave identical results to those obtained by DNA oligotyping in 26/27 patients. The antibodies identified the shared epitope in 14/14 cases and the presence of an HLA-DRB1*04 molecule in 12/12 cases. HLA-DRB1*0404 was identified in 4/4 cases. HLA-DRB1*0401 was identified in 5/6 cases. One patient oligotyped as HLA-DRB1*0401, but consistently failed to react with the *0401 Mab. DNA sequencing of the second exon of the HLA-DRB1*0401 allele in this patient confirmed a normal HLA-DRB1*0401 genotype.
CONCLUSIONS—FACS analysis of PBMNC stained with Mab recognising the shared epitope and rheumatoid arthritis associated HLA susceptibility molecules provides a rapid, reliable, and more accessible alternative to DNA oligotyping. The apparent discordance between phenotypic and genetic analysis of HLA-DRB1*0401 in one patient, may reflect variability in HLA-DRB1*0401 gene expression or in class II peptide presentation.
相似文献
30.
Ether lipids (EL) and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemic cells. In this study, the combined effects of EL (ET-18-OCH3, ET-16-NHCOCH3, or BM 41.440) and hyperthermia on the growth of hematopoietic progenitors, myeloid leukemic cell lines, and leukemic cells obtained from patients with acute myeloid leukemia (AML) were examined to determine if this combination resulted in a greater selective killing of leukemic cells than that achieved by either EL or heat alone. When the cells were treated simultaneously with EL (50 micrograms/mL) and hyperthermia (42 degrees C) for one hour, the killing of leukemic cell line cells was enhanced considerably. Among the three EL, however, the combination of ET-18-OCH3 and heat seemed to be the most cytotoxic to leukemic cell line cells with no effect on the growth of hematopoietic progenitors. An increase in the duration of treatment with ET-18-OCH3 to four hours with heat added during the last hour resulted in a further reduction of leukemic cell line cells while sparing 50% of hematopoietic progenitors after cryopreservation. The combined treatment with ET-18-OCH3 and heat also inhibited the growth of leukemic progenitors obtained from AML patients by 97% to 100%. These data indicate that the combined treatment with EL and hyperthermia might offer an efficient means to eliminate myeloid leukemic cells in vitro. 相似文献