全文获取类型
收费全文 | 664篇 |
免费 | 28篇 |
国内免费 | 1篇 |
专业分类
儿科学 | 52篇 |
妇产科学 | 11篇 |
基础医学 | 58篇 |
口腔科学 | 19篇 |
临床医学 | 77篇 |
内科学 | 130篇 |
皮肤病学 | 7篇 |
神经病学 | 17篇 |
特种医学 | 153篇 |
外科学 | 54篇 |
综合类 | 9篇 |
预防医学 | 42篇 |
眼科学 | 4篇 |
药学 | 32篇 |
肿瘤学 | 28篇 |
出版年
2021年 | 7篇 |
2019年 | 3篇 |
2018年 | 11篇 |
2017年 | 3篇 |
2016年 | 8篇 |
2015年 | 10篇 |
2014年 | 15篇 |
2013年 | 20篇 |
2012年 | 14篇 |
2011年 | 16篇 |
2010年 | 31篇 |
2009年 | 23篇 |
2008年 | 13篇 |
2007年 | 18篇 |
2006年 | 4篇 |
2005年 | 17篇 |
2004年 | 9篇 |
2003年 | 12篇 |
2002年 | 6篇 |
2001年 | 9篇 |
2000年 | 17篇 |
1999年 | 10篇 |
1998年 | 32篇 |
1997年 | 27篇 |
1996年 | 25篇 |
1995年 | 26篇 |
1994年 | 27篇 |
1993年 | 20篇 |
1992年 | 10篇 |
1991年 | 7篇 |
1990年 | 17篇 |
1989年 | 21篇 |
1988年 | 21篇 |
1987年 | 17篇 |
1986年 | 11篇 |
1985年 | 19篇 |
1984年 | 11篇 |
1983年 | 10篇 |
1982年 | 20篇 |
1981年 | 12篇 |
1980年 | 10篇 |
1978年 | 7篇 |
1977年 | 8篇 |
1976年 | 14篇 |
1975年 | 8篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1972年 | 3篇 |
1970年 | 6篇 |
1956年 | 4篇 |
排序方式: 共有693条查询结果,搜索用时 15 毫秒
11.
Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols 总被引:47,自引:7,他引:47
In order to study the biological activities of tea preparations and
purified tea polyphenols, their growth inhibitory effects were investigated
using four human cancer cell lines. Growth inhibition was measured by
[3H]thymidine incorporation after 48 h of treatment. The green tea
catechins (-)-epigallocatechin-3-gallate (EGCG) and (-)- epigallocatechin
(EGC) displayed strong growth inhibitory effects against lung tumor cell
lines H661 and H1299, with estimated IC50 values of 22 microM, but were
less effective against lung cancer cell line H441 and colon cancer cell
line HT-29 with IC50 values 2- to 3- fold higher.
(-)-Epicatechin-3-gallate, had lower activities, and (-)- epicatechin was
even less effective. Preparations of green tea polyphenols and theaflavins
had higher activities than extracts of green tea and decaffeinated green
tea. The results suggest that the growth inhibitory activity of tea
extracts is caused by the activities of different tea polyphenols. Exposure
of H661 cells to 30 microM EGCG, EGC or theaflavins for 24 h led to the
induction of apoptosis as determined by an annexin V apoptosis assay,
showing apoptosis indices of 23, 26 and 8%, respectively; with 100 microM
of these compounds, the apoptosis indices were 82, 76 and 78%,
respectively. Incubation of H661 cells with EGCG also induced a
dose-dependent formation of H2O2. Addition of H2O2 to H661 cells caused
apoptosis in a manner similar to that caused by EGCG. The EGCG-induced
apoptosis in H661 cells was completely inhibited by exogenously added
catalase (50 units/ml). These results suggest that tea polyphenol-induced
production of H2O2 may mediate apoptosis and that this may contribute to
the growth inhibitory activities of tea polyphenols in vitro.
相似文献
12.
Erythropoietic activity is known to be closely associated with marrow iron uptake. A modification of the standard measure of plasma iron turnover has been developed in which erythron transferrin uptake (ETU) rather than iron uptake has been calculated. The ETU has the advantage of providing a parameter of erythroid marrow activity independent of change produced by plasma iron and transferrin saturation. Measurements in 80 patients with anemia were compared to the normal value of 60 +/- 12 mumol/L whole blood/d. The mean ETU for ten patients with severe aplastic anemia and for six patients with pure red-cell aplasia were 12 +/- 8 and 12 +/- 11 mumol/L whole blood/d, respectively. In ten transfusion-dependent patients with renal failure under dialysis therapy, the mean value was 35 +/- 11, while ten other dialyzed patients who were transfusion independent had a mean ETU of 73 +/- 21 mumol/L whole blood/d. Sixteen patients with hemolytic anemia had an average ETU of 400 +/- 130, while 28 patients with ineffective erythropoiesis had a mean value of 474 +/- 147 mumol/L whole blood/d. While patients with hypoproliferative anemia showed no relation between the severity of anemia and ETU, those with hyperproliferative erythroid marrow showed increasing values as the anemia became more severe. Sequential measurements in patients with aplastic anemia under treatment and in thalassemic patients under transfusion therapy showed the value of this measurement in monitoring the effects of treatment on erythroid marrow activity. It is concluded that the measurement of ETU provides a more direct ferrokinetic evaluation of erythroid activity in anemic states. 相似文献
13.
Human interleukin-5 (IL-5) regulates the production of eosinophils in human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL-6, and GMCSF 总被引:33,自引:1,他引:33
Recombinant human interleukin-5 (rhIL-5), in either liquid or semi- solid cultures, selectively induced eosinophil production from normal human bone marrow, with no activity on other cell lineages. The time course of eosinophil production induced by murine IL-5, rhIL-3, and rh granulocyte-macrophage colony stimulating factor (GMCSF) was similar to rhIL-5. The rate of eosinophil maturation in vitro was independent of the stimulating cytokine, mature eosinophils being produced after 4 to 5 weeks in liquid culture with each of these cytokines. The eosinophils produced in response to each cytokine were morphologically indistinguishable, and had the ultrastructural features of maturity except that the electron-dense material in the granules had not formed into crystalline cores. Neither rhIL-1 nor rhIL-6 alone, or in combination with rhIL-5 or rhIL-3, induced eosinophil differentiation or proliferation under the conditions used. rhIL-3 and rhGMCSF induced more eosinophil colonies than rhIL-5, rhIL-5 had an additive, not synergistic, effect on eosinophil colony production when combined with either rhIL-3 or rhGMCSF, suggesting that rhIL-5 stimulates a smaller and possibly different population of eosinophil progenitors. However, rhIL-5 induced the greatest eosinophil production in liquid cultures, suggesting that although it may act on a smaller population of precursors, it is able to stimulate more proliferative steps than either rhIL-3 or rhGMCSF. 相似文献
14.
Charlotte W Ockeloen Marjolein H Willemsen Sonja de Munnik Bregje WM van Bon Nicole de Leeuw Aad Verrips Sarina G Kant Elizabeth A Jones Han G Brunner Rosa LE van Loon Eric EJ Smeets Mieke M van Haelst Gijs van Haaften Ann Nordgren Helena Malmgren Giedre Grigelioniene Sascha Vermeer Pedro Louro Lina Ramos Thomas JJ Maal Celeste C van Heumen Helger G Yntema Carine EL Carels Tjitske Kleefstra 《European journal of human genetics : EJHG》2015,23(9):1270-1185
Loss-of-function variants in ANKRD11 were identified as the cause of KBG syndrome, an autosomal dominant syndrome with specific dental, neurobehavioural, craniofacial and skeletal anomalies. We present the largest cohort of KBG syndrome cases confirmed by ANKRD11 variants reported so far, consisting of 20 patients from 13 families. Sixteen patients were molecularly diagnosed by Sanger sequencing of ANKRD11, one familial case and three sporadic patients were diagnosed through whole-exome sequencing and one patient was identified through genomewide array analysis. All patients were evaluated by a clinical geneticist. Detailed orofacial phenotyping, including orthodontic evaluation, intra-oral photographs and orthopantomograms, was performed in 10 patients and revealed besides the hallmark feature of macrodontia of central upper incisors, several additional dental anomalies as oligodontia, talon cusps and macrodontia of other teeth. Three-dimensional (3D) stereophotogrammetry was performed in 14 patients and 3D analysis of patients compared with controls showed consistent facial dysmorphisms comprising a bulbous nasal tip, upturned nose with a broad base and a round or triangular face. Many patients exhibited neurobehavioural problems, such as autism spectrum disorder or hyperactivity. One-third of patients presented with (conductive) hearing loss. Congenital heart defects, velopharyngeal insufficiency and hip anomalies were less frequent. On the basis of our observations, we recommend cardiac assessment in children and regular hearing tests in all individuals with a molecular diagnosis of KBG syndrome. As ANKRD11 is a relatively common gene in which sequence variants have been identified in individuals with neurodevelopmental disorders, it seems an important contributor to the aetiology of both sporadic and familial cases. 相似文献
15.
Clonal dysregulation of the antibody response to tetanus-toxoid after bone marrow transplantation 总被引:2,自引:0,他引:2
Gerritsen EJ; Van Tol MJ; Van 't Veer MB; Wels JM; Khouw IM; Touw CR; Jol-Van Der Zijde CM; Hermans J; Rumke HC; Radl J 《Blood》1994,84(12):4374-4382
After bone marrow transplantation (BMT), a prolonged dysregulation of humoral immunity can be observed. In the present study, we investigated whether this is reflected in an abnormal production of specific antibodies (Ab) to the T-cell-dependent recall antigen tetanus-toxoid (TT). The study group consisted of children receiving transplants of an unmodified allogeneic graft and of adults receiving either a T-cell- depleted allogeneic or an unmodified autologous BM graft. Findings were compared with those in healthy controls. In pediatric graft recipients, who were routinely revaccinated early after BMT, the Ab response was quantitatively superior to that in adult graft recipients who did not receive early revaccination. In the majority of graft recipients, the time period after vaccination required to reach the peak level of antibodies was prolonged and the number of responding TT-specific B- cell clones was markedly decreased in comparison with controls. In controls, a low frequency of dominant B-cell clones may produce low quantities of homogeneous Ab components (H-Ab) against a heterogeneous background. However, in BM graft recipients, "overshooting" of Ab production by separate B-cell clones was observed, resulting in the development of H-Ab at a relatively high concentration. These abnormalities were present up to 10 years after BMT, irrespective of either the age of the recipient, the modulation of the graft, or the vaccination schedule used. It is hypothesized that the dysregulated Ab production is the consequence of activation of a restricted number of resting memory B cells, present in germinal centers, repopulating gradually after BMT. Our data show that routine revaccination early after BMT improves the humoral immune response. However, because of a clonally dysregulated Ab production, long-lasting qualitative defects may be present even after normalization of Ab titers. 相似文献
16.
IgG autoantibodies eluted from RBCs of antiglobulin positive normal blood donors contained at least two antibody populations, an IgG autoantibody (Ab 1), and an IgG population (Ab 2) that agglutinated RBCs coated with some Rh(D) alloantibodies. Eight of 24 autoantibody eluates tested agglutinated 3 of 10 anti-Rh(D) sensitized RBCs. The agglutinating activity was inhibited specifically by preincubation of the autoantibody eluate with the reactive anti-D. The reaction did not require the Fc domain of the anti-Rh(D), since autoantibody eluates agglutinated RBCs coated with F(ab')2 prepared from the reactive anti-D sera. These findings indicate that the RBCs of some antiglobulin- positive blood donors contain an immunoglobulin auto-antiidiotype (Ab 2) against the RBC autoantibody (Ab 1) which is demonstrable through its cross-reactivity with selected Rh(D) alloantibodies. Identification of auto-antiidiotypes in RBC autoimmunity lends support to the idiotype- antiidiotype network hypothesis of immune regulation and is consistent with the bizarre and complex serology of autoimmune hemolytic anemia. The absence of clinical hemolysis in antiglobulin-positive normal blood donors suggests that immunoglobulin idiotype-antiidiotype interactions may play a role in modulating the effects of RBC autoimmunity. 相似文献
17.
Hemostatic plug (HP) formation was investigated in the ear bleeding time incision in normal and von Willebrand pigs. HP volume was calculated by integrating the areas of serial sections. In normal pigs (n = 11), platelets immediately formed a layer on the surface of the cut channel. Platelet aggregates formed at the ends of transected vessels and gradually enlarged. Finally, all transected vessels were occluded by HP and bleeding stopped. In contrast, large HPs were formed in the incision in von Willebrand's disease (vWD) pigs (n = 4); these HPs did not cover the ends of the transected vessels, which continued to bleed, allowing the formation of large hemostatically ineffective platelet aggregates in the incision. Canals traversed these HPs, and bleeding from the open vessels may have continued through them. After infusion of cryoprecipitate into a vWD pig, the bleeding time shortened, and the morphological findings of the HPs were similar to those of normal pigs. In normal pigs (n = 3) infused with an anti- Willebrand factor monoclonal antibody, which prolonged the bleeding time, a large HP formed in the incision, similar to that observed in the vWD pig. The volume of the normal and vWD HPs increased with time. These in vivo findings suggest that Willebrand factor is involved in the localization of the HP to the damaged vessel and may also play a role in platelet-platelet interaction. A computerized morphometric technique was used for measuring the volume of the hemostatic plugs and the distance of sequential points on the perimeter of the HP from the center of selected bleeding vessels. 相似文献
18.
Corzo D; Yunis JJ; Salazar M; Lieberman JA; Howard A; Awdeh Z; Alper CA; Yunis EJ 《Blood》1995,86(10):3835-3840
Genes of the major histocompatibility complex (MHC) have been associated with susceptibility to drug-induced adverse reactions. We previously found that clozapine-induced agranulocytosis (CA) is associated with the HLA-DRB1*0402, DRB4*0101, DQB1*0302, DQA1*0301 haplotype in Ashkenazi Jewish patients and with the HLA-DRB1*1601, DRB5*02, DQB1*0502, DQA1*0102 haplotype in non-Jewish patients. In the present study, we tested the hypothesis that the variants of the heat- shock protein 70 (HSP-70) encoded by the HSP-70 loci located within the MHC region and known to be involved in apoptosis and regulation of cell proliferation could play an important role in molecular mechanisms of CA. First, we analyzed HSP70-2 polymorphism in risk-associated haplotypes from HLA homozygous cells and normal individuals and confirmed that the HSP70-2 9-kb variant was associated invariably with DR4 (HLA-DRB1*0402, DQB1*0302) and DR2 (HLA-DRB1*01601, DQB1*0502, DQA1*0102 and HLA-DRB1*1501, DQB1*0602) haplotypes, which were the haplotypes found increased in Jewish and non-Jewish patients with CA, respectively. The 9.0-kb variant was also found to be associated with HLA-B44, DRB1*0401 and HLA-B44, DRB1*07 haplotypes. Second, in patients with CA (12 Ashkenazi Jewish and 20 non-Jewish patients), HSP70-1 A and HSP70-2 9.0-kb variants were associated with the MHC haplotypes found by us to be markers of susceptibility to CA. The clozapine-treated control group had an excess number of HSP70-1 C and HSP70-2 8.5-kb variants, consistent with genetic resistance to CA associated with those variants. This finding supports our hypothesis that a dominant gene within the MHC region (marked by HSP70-1 and HSP70-2), but not necessarily HLA, is associated with CA in two different ethnic groups. 相似文献
19.
Benjamin Buecking Daphne Eschbach Christopher Bliemel Ludwig Oberkircher Johannes Struewer Steffen Ruchholtz Ulrich J. Sachs 《Thrombosis research》2014
Introduction
Vitamin K antagonists are often used for anticoagulant treatment in hip fracture patients. The optimal handling with such anticoagulants is unclear.We aimed to determine when anticoagulation reversal occurred after vitamin K administration and how often prothrombin complex concentrates (PCCs) were administered. We compared patients’ treatments and outcomes with those of a control group not receiving treatment for anticoagulation.Patients and Methods
A total of 402 geriatric hip fracture patients were included in this observational study. We collected data on treatment for anticoagulation, time to surgery, and reasons for delay of surgery. In patients taking vitamin K antagonists, we measured the INR (international normalized ratio) on admission and prior to surgery, along with the frequency of PCC administration. Finally, we compared in-hospital mortality and complications between patient groups.Results
A total of 62 (15%) patients received phenprocoumon prior to their fractures. Surgery was delayed in these patients compared to controls (27 h; 95%CI 23–31 vs. 16 h; 95%CI 19–19; p = 0.001), but surgery delay > 48 h (n = 5; 8%) was not due to a failure of INR reversal. The main reason for these delays was a lack of capacity for surgery. The average INR on admission was 2.1 (± 0.7; range 1.0-3.5) in patients taking phenprocoumon, which decreased to 1.3 (± 0.3; range 1.0-1.6) until surgery. PCCs were administered to 19% of patients. We found no differences in the in-hospital mortality (6.2% vs. 8.1%, p = 0.575) or complication rates (12.9% vs. 9.4%, p = 0.364).Conclusion
The use of vitamin K seemed to be sufficient for anticoagulation reversal in geriatric hip fracture patients, and it generally led to timely surgery; despite this success, PCCs were sometimes administered for logistical reasons. 相似文献20.