全文获取类型
收费全文 | 2080篇 |
免费 | 123篇 |
国内免费 | 10篇 |
专业分类
耳鼻咽喉 | 63篇 |
儿科学 | 124篇 |
妇产科学 | 173篇 |
基础医学 | 186篇 |
口腔科学 | 146篇 |
临床医学 | 151篇 |
内科学 | 330篇 |
皮肤病学 | 66篇 |
神经病学 | 142篇 |
特种医学 | 58篇 |
外科学 | 335篇 |
综合类 | 46篇 |
预防医学 | 73篇 |
眼科学 | 86篇 |
药学 | 91篇 |
中国医学 | 54篇 |
肿瘤学 | 89篇 |
出版年
2024年 | 2篇 |
2023年 | 37篇 |
2022年 | 54篇 |
2021年 | 75篇 |
2020年 | 39篇 |
2019年 | 69篇 |
2018年 | 78篇 |
2017年 | 74篇 |
2016年 | 104篇 |
2015年 | 82篇 |
2014年 | 114篇 |
2013年 | 122篇 |
2012年 | 161篇 |
2011年 | 181篇 |
2010年 | 94篇 |
2009年 | 111篇 |
2008年 | 155篇 |
2007年 | 146篇 |
2006年 | 138篇 |
2005年 | 114篇 |
2004年 | 84篇 |
2003年 | 75篇 |
2002年 | 47篇 |
2001年 | 14篇 |
2000年 | 4篇 |
1999年 | 6篇 |
1998年 | 5篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1991年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1979年 | 2篇 |
1977年 | 1篇 |
1968年 | 1篇 |
1966年 | 2篇 |
排序方式: 共有2213条查询结果,搜索用时 31 毫秒
91.
Effects of imatinib vary with the types of KIT-mutation in gastrointestinal stromal tumor cell lines 总被引:1,自引:0,他引:1
Noma K Naomoto Y Gunduz M Matsuoka J Yamatsuji T Shirakawa Y Nobuhisa T Okawa T Takaoka M Tomono Y Hiroyuki O Gunduz E Tanaka N 《Oncology reports》2005,14(3):645-650
Mutations of proto-oncogene c-kit in gastrointestinal stromal tumors (GISTs) are considered to cause a constitutive activation of KIT responsible for their oncogenesis. Imatinib has therapeutic potential for GISTs because of its inhibitory effect on KIT kinase activity. However, no study has been published concerning the effects of imatinib on GIST cells with various types of KIT mutation. To investigate the effects of imatinib on various c-kit mutations found in GISTs, cell proliferation and apoptosis assays were performed in two GIST cell lines with different KIT mutations. One of the cell lines, GIST-T1, revealed a heterozygous deletion of exon 11 in the c-kit, while the other cell line, GIST882, possessed a homozygous missense mutation of exon 13 in the c-kit gene. Imatinib inhibited proliferation and induced apoptosis in both cell lines. Imatinib potently suppressed proliferation of the GIST882 cell line at the concentration of 1.0 microM, whereas it inhibited the GIST-T1 at 0.1 microM. In two types of activating mutant KIT, imatinib could inhibit the constitutive activation of both types of KIT mutant, although the antiproliferative effect on GIST882 was weaker than on GIST-T1. Western blot analysis revealed that apoptosis related proteins were activated or suppressed by imatinib in both cell lines in the respective manner. Our results suggest that the apoptotic signal trans-duction caused by imatinib in GISTs is susceptible to various types of KIT mutation. 相似文献
92.
Oncolytic therapy is a novel anticancer treatment with attenuated lytic viruses such as adenovirus (Ad). These viruses kill the host cells through their lytic replication cycle and are thus distinct from classical gene therapy viruses, which serve as gene delivery agents and do not replicate. Oncolytic Ads are genetically engineered so as to replicate only in cancer cells. Their replication cycle leads to viral multiplication, the killing of the host cells and spreading of the infection throughout the tumor. Following success in preclinical studies, their anti-tumor potential is now being evaluated in the clinic. Three oncolytic Ads (dl1520, Ad5-CD/TKrep, and CV706) have completed Phase I and II clinical trials in cancer patients where their administration via multiple routes and in combination with chemo- or radiotherapies, has demonstrated overall safety. These viruses are being re-engineered to arm them with additional therapeutic genes, bolstering their oncolytic activity with a bystander effect. For example, Ad5-CD/TKrep delivers a therapeutic prodrug-activating (suicide) gene. These data indicate that oncolytic Ads are a promising novel cancer treatment approach that can be combined with other modalities, such as gene therapy and classical chemo- and radiotherapies. Further improvements to enhance their specificity, targeting and oncolytic activity are needed however, as these first-generation viruses showed modest anti-tumor activity. To improve their efficacy in the clinic, it will be important to devise and incorporate novel monitoring techniques in the clinical trials, such as analysis of viral replication in biopsies and through the use of creative noninvasive imaging technologies. 相似文献
93.
Trefoil factor expression in biliary epithelium of graft-versus-host disease of the liver after allogeneic hematopoietic cell transplantation 总被引:1,自引:0,他引:1
Idilman R Erden E Arat M Soydan E Erkan O Kuzu I Sahin Y Coban S Bozdayi M Giraud A Akan H Karayalcin S Ozden A 《Transplantation》2005,80(8):1099-1104
BACKGROUND: The aims of this study were to determine the presence of trefoil factor family-3 (TFF3) expression in biliary epithelial cells (BECs) of chronic graft-versus-host disease (cGVHD) of the liver after allogeneic hematopoietic cell transplantation, to compare such expression in chronic liver diseases (CLD) with/without predominantly biliary disease, and to assess the effect of bile duct injury on the degree of TFF3 expression in BECs of cGVHD. METHODS: A total of 82 paraffin-embedded liver biopsy samples were reviewed. These samples were basically divided into two distinct groups according to the presence of ductal injury: group 1 with CLD and predominantly biliary disease (n=26: 17 cGVHD and 9 primary biliary cirrhosis [PBC]) and group 2 with CLD and predominantly parenchymal liver disease (n=56: 20 steatohepatitis and 36 chronic viral hepatitis). Group 2 was used as the controls. Immunohistochemistry was performed using a polyclonal anti-TFF3 antibody. Real-time quantitative PCR was used for the detection of TFF3 mRNA expression. RESULTS: Positive TFF3 immunohistochemical staining and the presence of TFF3 messenger RNA gene expression was demonstrably higher in group 1 than that in group 2 (P<0.0001 and P<0.05, respectively). No significant difference in terms of positive TFF3 stained BECs between GVHD and PBC samples was observed (P>0.05). The extent of TFF3 expression in GVHD samples with severe ductal injury were significantly more common than that of GVHD samples with mild/moderate ductal injury (P<0.0001). CONCLUSIONS: The expression of TFF3 in cGVHD of the liver is increased in response to bile duct damage and repair. Such expression seems to be related the severity of ductal injury. 相似文献
94.
95.
96.
Demirkilic U Gunay C Bolcal C Doganci S Cingoz F Kuralay E Tatar H 《Journal of cardiac surgery》2005,20(2):124-128
AIM: To delineate whether coronary arteriovenous malformations have different properties than classical discrete coronary artery fistulae. METHODS: Group 1 included 17 patients with discrete coronary fistula that represents a coronary artery fistula draining into any cardiac chamber. Group 2 included six patients with coronary arteriovenous malformations representing extensive coronary artery malformation. Cardiopulmonary bypass was used in 12 of the Group 1 patients and 5 in Group 2. RESULTS: There was no operative mortality in either group. Following a hemodynamically nonsignificant residual fistulous communication, which was detected by repeat coronary angiography in Group 2; we changed our surgical technique of suture ligation on beating heart. Then we preferred pulmonary arteriotomy and sutured the orifice of coronary arteriovenous malformations from within the chamber. CONCLUSIONS: Coronary arteriovenous malformations have different morphology and also complex progression properties when compared with discrete coronary artery fistulae. Surgical repair of coronary arteriovenous malformation should be done by suturing the multiple drainage holes inside the draining chamber. Suture ligation of coronary arteriovenous malformation is difficult due to the fragile vessel. 相似文献
97.
Cengiz N Baskin E Anarat R Agras PI Yildirim SV Tiker F Anarat A Saatci U 《Pediatric nephrology (Berlin, Germany)》2005,20(7):937-939
It has been suggested that urinary glycosaminoglycans (GAGs) form a natural defense mechanism against urinary tract infections (UTIs). This study investigated whether urinary GAGs play a role in pediatric UTIs, and whether urinary GAG level can be used to differentiate upper UTI from lower UTI. Forty-one children with UTIs (33 girls and eight boys; mean age 5.4+/-3.7 years) and 46 age- and sex-matched healthy children (35 girls and 11 boys; mean age 6.6+/-3.9 years) were included in the study. Urinary GAG levels were measured at the onset of acute infection and after a 10-day course of antibiotic treatment. Group GAG findings were compared, and comparisons were also made with the patients divided according to sex and according to UTI type (upper versus lower). The mean urinary GAG level in the patient group at the onset of acute infection (pretreatment) was significantly higher than the mean level in the control group (132.2+/-104.8 mg/g vs 42.2+/-27.1 mg/g creatinine, respectively; P <0.01). In the patient group, the mean urinary GAG level after antimicrobial therapy was significantly lower than the pretreatment level (75.9+/-52.1 mg/g vs 132.2+/-104.8 mg/g creatinine, respectively; P <0.01). However, the mean post-treatment level was still higher than the mean level in the controls ( P <0.05). There was no significant difference in urinary GAG levels when patients were categorized as upper versus lower UTI ( P >0.05). The study results suggest that GAGs play an important role in the pathogenesis of UTIs in children, and that measurement of urinary GAGs may be a valuable noninvasive method for evaluating UTIs in this patient group. However, this assay cannot be used to differentiate upper UTI from lower UTI in children. 相似文献
98.
The aim of this study was to determine the effect of a mechanical bowel preparation on postoperative surgical wound infections
in patients treated with identical antimicrobial prophylaxis undergoing wide excision and primary closure for chronic pilonidal
sinus disease. Patients more than 18 years old were included in the study. All patients had intravenous antimicrobial prophylaxis
at the time of anesthesia induction. In a prospective, randomized setting, patients were allocated to either the bowel preparation
group or the no-bowel-preparation group. Mechanical bowel preparation was performed using an oral sodium phosphate solution.
On the morning of the procedure a rectal enema was performed with the phosphate solution. The primary outcome measure was
the rate of wound infection, but all postoperative complications and recurrences were recorded. All patients were actively
observed for 1 year after discharge. The overall infection rate for the entire study population was 12.8% (13/101) including
14.3% (7/49) of those who had had the bowel preparation and 11.5% (6/52) of those with no bowel preparation. There was no
statistically significant difference between groups (P = 0.680). The mean rate of recurrence for all 101 patients was 4.9% (5/101) at 19.2 months (range 12–32 months) of follow-up.
The recurrence rate was 6.1% (3/49) in the bowel preparation group and 3.8% (2/52) in the no-bowel-preparation group (P = 1.000). Although the number of patients is small in this study, our results showed that the mechanical bowel preparation
does not cause a decrease in the rate of surgical wound infections after excision and primary closure in patients with chronic
pilonidal sinus disease. 相似文献
99.
Brakefield PM Gems D Cowen T Christensen K Grubeck-Loebenstein B Keller L Oeppen J Rodriguez-Pena A Stazi MA Tatar M Westendorp RG 《Mechanisms of ageing and development》2005,126(3):431-438
An open issue in research on ageing is the extent to which responses to the environment during development can influence variability in life span in animals, and the health profile of the elderly in human populations. Both affluence and adversity in human societies have profound impacts on survivorship curves, and some of this effect may be traceable to effects in utero or in infancy. The Barker Hypothesis that links caloric restriction in very early life to disruptions of glucose-insulin metabolism in later life has attracted much attention, as well as some controversy, in medical circles. It is only rarely considered by evolutionary biologists working on phenotypic plasticity, or by biogerontologists studying model organisms such as C. elegans or Drosophila. One crucial mechanism by which animals can respond in an adaptive manner to adverse conditions, for example in nutrition or infection, during development is phenotypic plasticity. Here we begin with a discussion of adaptive plasticity in animals before asking what such phenomena may reveal of relevance to rates of ageing in animals, and in humans. We survey the evidence for effects on adult ageing of environmental conditions during development across mammalian and invertebrate model organisms, and ask whether evolutionary conserved mechanisms might be involved. We conclude that the Barker Hypothesis is poorly supported and argue that more work in human populations should be integrated with multi-disciplinary studies of ageing-related phenomena in experimental populations of different model species that are subjected to nutritional challenges or infections during pre-adult development. 相似文献
100.
Ozer EA Kumral A Ozer E Yilmaz O Duman N Ozkal S Koroglu T Ozkan H 《Pediatric research》2005,58(1):38-41
Pulmonary oxygen toxicity is believed to play a prominent role in the lung injury that leads to the development of bronchopulmonary dysplasia (BPD). To determine whether human recombinant erythropoietin (rhEPO) treatment reduces the risk of developing BPD, we investigated the effect of rhEPO treatment on the histopathologic changes seen in hyperoxia-induced lung injury of BPD. Twenty-five rat pups were divided into four groups: air-exposed control group (n = 5), hyperoxia-exposed placebo group (n = 7), hyperoxia-exposed rhEPO-treated group (n = 6), and air-exposed rhEPO-treated group (n = 7). Measurement of alveolar surface area, quantification of secondary crest formation, microvessel count, evaluation of alveolar septal fibrosis, and smooth muscle actin immunostaining were performed to assess hyperoxia-induced changes in lung morphology. Treatment of hyperoxia-exposed animals with rhEPO resulted in a significant increase in the mean alveolar area, number of secondary crests formed, and the microvessel count in comparison with hyperoxia-exposed placebo-treated animals. There was significantly less fibrosis in rhEPO-treated animals. However, treatment of hyperoxia-exposed animals with rhEPO did not result in a significant change in smooth muscle content compared with hyperoxia-exposed placebo treated animals. Our results suggest treatment with rhEPO during hyperoxia exposure is associated with improved alveolar structure, enhanced vascularity, and decreased fibrosis. Therefore, we conclude that treatment of preterm infants with EPO might reduce the risk of developing BPD. 相似文献