全文获取类型
收费全文 | 782篇 |
免费 | 29篇 |
国内免费 | 11篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 49篇 |
妇产科学 | 34篇 |
基础医学 | 95篇 |
口腔科学 | 11篇 |
临床医学 | 69篇 |
内科学 | 188篇 |
皮肤病学 | 13篇 |
神经病学 | 7篇 |
特种医学 | 136篇 |
外科学 | 70篇 |
综合类 | 13篇 |
预防医学 | 52篇 |
眼科学 | 8篇 |
药学 | 36篇 |
1篇 | |
中国医学 | 6篇 |
肿瘤学 | 30篇 |
出版年
2022年 | 4篇 |
2021年 | 5篇 |
2018年 | 11篇 |
2017年 | 4篇 |
2016年 | 6篇 |
2015年 | 8篇 |
2014年 | 14篇 |
2013年 | 15篇 |
2012年 | 17篇 |
2011年 | 18篇 |
2010年 | 28篇 |
2009年 | 26篇 |
2008年 | 22篇 |
2007年 | 21篇 |
2006年 | 27篇 |
2005年 | 19篇 |
2004年 | 15篇 |
2003年 | 25篇 |
2002年 | 18篇 |
2001年 | 22篇 |
2000年 | 17篇 |
1999年 | 21篇 |
1998年 | 37篇 |
1997年 | 31篇 |
1996年 | 47篇 |
1995年 | 48篇 |
1994年 | 38篇 |
1993年 | 20篇 |
1992年 | 5篇 |
1991年 | 15篇 |
1990年 | 13篇 |
1989年 | 20篇 |
1988年 | 29篇 |
1987年 | 18篇 |
1986年 | 16篇 |
1985年 | 20篇 |
1984年 | 13篇 |
1983年 | 9篇 |
1982年 | 8篇 |
1981年 | 9篇 |
1980年 | 9篇 |
1979年 | 7篇 |
1978年 | 7篇 |
1977年 | 7篇 |
1976年 | 7篇 |
1975年 | 6篇 |
1973年 | 4篇 |
1971年 | 2篇 |
1967年 | 3篇 |
1965年 | 2篇 |
排序方式: 共有822条查询结果,搜索用时 31 毫秒
11.
Th. Schmeiser W. Heit R. Arnold D. Bunjes M. Wiesneth B. Hertenstein W. Hampl H. Heimpel 《Journal of molecular medicine (Berlin, Germany)》1987,65(20):967-974
Summary Conditioning therapy with aggressive chemotherapy and irradiation induces a state of transient combined immunodeficiency in bonemarrow transplant recipients. This promotes the occurrence of severe cytomegalovirus (CMV) infections, the most frequent lethal complication after bone-marrow transplantation (BMT) at present.Forty-four BMT recipients received CMV-IgG-hyperimmunoglobulin for CMV prophylaxis intravenously. The efficacy of this prophylaxis and possible risk factors for the occurrence of CMV-induced interstitial pneumonia (IP) were analyzed. Risk factors for the promotion of a CMV-IP were: additional immunosuppressive therapy after BMT, CMV-positive serostatus of the recipient, CMV-seropositive granulocyte transfusion, CMV infection immediately prior to BMT, and HLA-haploidentical BMT. In this study the incidence of graftversus-host disease was low and was not associated with the incidence of CMV infections. The use of T-cell-depleted grafts did not result in increased CMV infections or IP and may possibly have improved the immunological reconstitution.Abbreviations BMT
Bone-marrow transplantation
- CMV
Cytomegalovirus
- CMV-IG
CMV-IgG-hyperimmunoglobulin
- GvHD
Graft-versus-host disease
- IP
Interstitial pneumonia
- IS
Immunosuppressive therapy 相似文献
12.
Expression and potential role of fibroblast growth factor 2 and its receptors in human embryonic stem cells 总被引:7,自引:0,他引:7
Dvorak P Dvorakova D Koskova S Vodinska M Najvirtova M Krekac D Hampl A 《Stem cells (Dayton, Ohio)》2005,23(8):1200-1211
Although the detection of several components of the fibroblast growth factor (FGF) signaling pathway in human embryonic stem cells (hESCs) has been reported, the functionality of that pathway and effects on cell fate decisions are yet to be established. In this study we characterized expression of FGF-2, the prototypic member of the FGF family, and its receptors (FGFRs) in undifferentiated and differentiating hESCs; subsequently, we analyzed the effects of FGF-2 on hESCs, acting as both exogenous and endogenous factors. We have determined that undifferentiated hESCs are abundant in several molecular-mass isoforms of FGF-2 and that expression pattern of these isoforms remains unchanged under conditions that induce hESC differentiation. Significantly, FGF-2 is released by hESCs into the medium, suggesting an autocrine activity. Expression of FGFRs in undifferentiated hESCs follows a specific pattern, with FGFR1 being the most abundant species and other receptors showing lower expression in the following order: FGFR1 --> FGFR3 --> FGFR4 --> FGFR2. Initiation of differentiation is accompanied by profound changes in FGFR expression, particularly the upregulation of FGFR1. When hESCs are exposed to exogenous FGF-2, extracellular signal-regulated kinases are phosphorylated and thereby activated. However, the presence or absence of exogenous FGF-2 does not significantly affect the proliferation of hESCs. Instead, increased concentration of exogenous FGF-2 leads to reduced outgrowth of hESC colonies with time in culture. Finally, the inhibitor of FGFRs, SU5402, was used to ascertain whether FGF-2 that is released by hESCs exerts its activities via autocrine pathways. Strikingly, the resultant inhibition of FGFR suppresses activation of downstream protein kinases and causes rapid cell differentiation, suggesting an involvement of autocrine FGF signals in the maintenance of proliferating hESCs in the undifferentiated state. In conclusion from our data, we propose that this endogenous FGF signaling pathway can be implicated in self-renewal or differentiation of hESCs. 相似文献
13.
SE Andrew 《Clinical genetics》2003,64(4):293-296
14.
15.
Debelenko LV; Brambilla E; Agarwal SK; Swalwell JI; Kester MB; Lubensky IA; Zhuang Z; Guru SC; Manickam P; Olufemi SE; Chandrasekharappa SC; Crabtree JS; Kim YS; Heppner C; Burns AL; Spiegel AM; Marx SJ; Liotta LA; Collins FS; Travis WD; Emmert-Buck MR 《Human molecular genetics》1997,6(13):2285-2290
Lung carcinoids occur sporadically and rarely in association with multiple
endocrine neoplasia type 1 (MEN1). There are no well defined genetic
abnormalities known to occur in these tumors. We studied 11 sporadic lung
carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene
on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy
fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was
studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene
were inactivated. All four tumors showed the presence of a MEN1 gene
mutation and loss of the other allele. Observed mutations included a 1 bp
insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide
substitution affecting a donor splice site. Each mutation predicts
truncation or potentially complete loss of menin. The remaining seven
tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH.
The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a
complex germline MEN1 gene mutation. The data implicate the MEN1 gene in
the pathogenesis of sporadic lung carcinoids, representing the first
defined genetic alteration in these tumors.
相似文献
16.
Dr. L. Stárka CSc Dr. R. Hampl CSc Dr. M. Bičíková Dr. J. Obenberger CSc 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》1976,199(3):261-266
Summary The occurrence of testosterone, estrone, and estradiol-17 in aqueous humor and vitreous body of the rabbit eye was demonstrated. The identity of the steroid hormones was confirmed by their chromatographic properties, microreactions, and radiochemically by crystallization to constant specific activity of their labeled acetates. The levels of testosterone and estrogens in rabbit male and female plasma, aqueous, and vitreous were determined by radioimmunologic assay. The concentrations of the steroid hormones in plasma are higher than in aqueous and vitreous. However, testosterone in aqueous circulates in free form and lacks the binding to sexual hormone-binding globulin as in plasma.
Zusammenfassung Bericht über das Vorkommen von Testosteron, Oestron und Oestradiol-17 im Kammerwasser und Glasörper des Kaninchenauges. Die Art der Steroide wurde mittels Chromatographie, Mikroreaktionen und radiochemisch ermittelt. Der Testosteron- und Oestrogenspiegel im männlichen und weiblichen Kaninchenplasma, im Kammerwasser und Glaskörper wurde radioimmunologisch bestimmt. Die Plasmakonzentration der Steroidhormone lag höher als diejenige im Kammerwasser oder Glaskörper. Testosteron zirkuliert jedoch im Kammerwasser in freier Form, im Plasma dagegen ist es überwiegend an Sexualhormonebindende Globuline gebunden.相似文献
17.
A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma 总被引:8,自引:2,他引:8
Chen J; Giovannucci E; Hankinson SE; Ma J; Willett WC; Spiegelman D; Kelsey KT; Hunter DJ 《Carcinogenesis》1998,19(12):2129-2132
We examined the relationship between a functional polymorphism (667C--
>T, ala-->val) of the methylenetetrahydrofolate reductase gene
(MTHFR) and the risk of colorectal adenomas in the prospective Nurses'
Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR
val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval
(CI) 0.84-2.17] was not significantly associated with risk of adenomas.
This lack of association was observed for both small (RR = 1.36, 95% CI
0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore,
there was no significant interaction between this polymorphism and
consumption of either folate, methionine or alcohol. We also examined the
relationship of a newly identified polymorphism (asp919gly) of the
methionine synthase gene (MS) with the risk of colorectal adenomas in the
same population. The MS gly/gly polymorphism was also not significantly
associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70).
These results, which need to be confirmed in other studies, suggest that
the MTHFR val/val polymorphism, which has been previously inversely
associated with risk of colorectal cancer, plays a role only in a late
stage (adenoma-- >carcinoma) of colorectal tumorigenesis, and/or may
protect against malignant transformation in the subset of benign adenomas,
which may progress to malignancy.
相似文献
18.
M Hampl J A Hampl P Schwarz S Frank M Hahn G Schackert H D Saeger H K Schackert 《Invasion & metastasis》1998,18(2):81-95
Tumor progression is characterized by stepwise accumulation of genetic alterations. To identify alterations associated with breast cancer metastasis, an analysis of comparative loss of heterozygosity (LOH) was performed on 38 primary sporadic breast carcinomas and 16 distant metastases. Two loci at 5q21 and 18q21 were chosen because of their reported increased deletion frequency in metastatic tumors. LOH at 17q21, 13q12-13, 17p13.1 and 11q22-23 was analyzed to determine whether there is a specific involvement of these breast cancer-associated gene loci in the metastatic process. Our data show that distant metastases are characterized by markedly increased LOH frequency at all loci examined. In both gene locus groups, significantly more distant metastases are affected by combined LOH. Furthermore, a significantly reduced postmetastatic survival time has been observed in patients with brain metastases affected by synchronous allelic loss at the four breast cancer-associated gene loci. Our results suggest that cumulative LOH of breast cancer-related gene loci is associated with a more aggressive phenotype of metastatic breast tumors. 相似文献
19.
Jan Vondrácek Miroslav Machala Vítezslav Bryja Katerina Chramostová Pavel Krcmár Cornelia Dietrich Ales Hampl Alois Kozubík 《Toxicological sciences》2005,83(1):53-63
Polychlorinated biphenyls (PCBs) exhibit tumor-promoting effects in experimental animals. We investigated effects of six model PCB congeners and hydroxylated PCB metabolites on proliferation of contact-inhibited rat liver epithelial WB-F344 cells. The 'dioxin-like' PCB congeners, PCB 126, PCB 105, and 4'-OH-PCB 79, a metabolite of the planar PCB 77 congener, induced cell proliferation in a concentration-dependent manner. In contrast, the 'non-dioxin-like' compounds that are not aryl hydrocarbon receptor (AhR) agonists, PCB 47, PCB 153, and 4-OH-PCB 187, an abundant noncoplanar PCB metabolite, had no effect on cell proliferation at concentrations up to 10 muM. The concentrations of dioxin-like PCBs leading to cell proliferation corresponded with the levels inducing the expression of cytochrome P450 1A1 mRNA, suggesting that the release from contact inhibition was associated with AhR activation. The effects of PCB 126 and PCB 153 on expression of proteins controlling G0/G1-S-phase transition and S-phase progression were compared. Only PCB 126 was found to upregulate cyclin A and D2 protein levels, and to increase both total cyclin-dependent kinase 2 (cdk2) and cyclin A/cdk2 complex activities. Despite the observed upregulation of cyclin D2, no increase in cdk4 activity was observed. The expression of cdk inhibitor p27Kip1 was not affected by either PCB 126 or PCB 153. These results suggest that dioxin-like PCBs can induce cell proliferation of contact-inhibited rat liver epithelial cells by increasing cyclin A protein levels, a process that then leads to upregulation of cyclin A/cdk2 activity and initiation of DNA replication. This mechanism could be involved in tumor-promoting effects of dioxin-like PCBs. 相似文献
20.