全文获取类型
收费全文 | 259篇 |
免费 | 34篇 |
专业分类
293篇 |
出版年
2022年 | 3篇 |
2021年 | 5篇 |
2017年 | 2篇 |
2016年 | 3篇 |
2015年 | 2篇 |
2014年 | 9篇 |
2013年 | 4篇 |
2012年 | 9篇 |
2011年 | 15篇 |
2010年 | 5篇 |
2009年 | 11篇 |
2008年 | 15篇 |
2007年 | 6篇 |
2006年 | 4篇 |
2005年 | 11篇 |
2004年 | 11篇 |
2003年 | 7篇 |
2002年 | 5篇 |
2001年 | 8篇 |
2000年 | 9篇 |
1999年 | 6篇 |
1998年 | 4篇 |
1996年 | 6篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 6篇 |
1991年 | 9篇 |
1990年 | 6篇 |
1989年 | 2篇 |
1988年 | 9篇 |
1987年 | 6篇 |
1986年 | 2篇 |
1985年 | 7篇 |
1984年 | 6篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1980年 | 6篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1974年 | 3篇 |
1973年 | 7篇 |
1969年 | 2篇 |
1967年 | 3篇 |
1966年 | 2篇 |
1965年 | 2篇 |
1961年 | 2篇 |
1956年 | 2篇 |
1955年 | 2篇 |
1932年 | 2篇 |
排序方式: 共有293条查询结果,搜索用时 15 毫秒
151.
152.
153.
Michele Heisler Timothy P Hofer Mandi L Klamerus Julie Schmittdiel Joe Selby Mary M Hogan Hayden B Bosworth Adam Tremblay Eve A Kerr 《Trials》2010,11(1):1-14
Background
Each year, worldwide about 530,000 women die from causes related to pregnancy and childbirth. Of the deaths 99% are in low and middle income countries. Obstetric haemorrhage is the leading cause of maternal mortality, most occurring in the postpartum period. Systemic antifibrinolytic agents are widely used in surgery to prevent clot breakdown (fibrinolysis) in order to reduce surgical blood loss. At present there is little reliable evidence from randomised trials on the effectiveness of tranexamic acid in the treatment of postpartum haemorrhage.Methods
The Trial aims to determine the effect of early administration of tranexamic acid on mortality, hysterectomy and other morbidities (surgical interventions, blood transfusion, risk of non-fatal vascular events) in women with clinically diagnosed postpartum haemorrhage. The use of health services and safety, especially thromboembolic effect, on breastfed babies will also be assessed. The trial will be a large, pragmatic, randomised, double blind, placebo controlled trial among 15,000 women with a clinical diagnosis of postpartum haemorrhage. All legally adult women with clinically diagnosed postpartum haemorrhage following vaginal delivery of a baby or caesarean section will potentially be eligible. The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use an antifibrinolytic agent in a particular woman with postpartum haemorrhage. Treatment will entail a dose of tranexamic acid (1 gram by intravenous injection) or placebo (sodium chloride 0.9%) will be given as soon as possible after randomisation. A second dose may be given if after 30 minutes bleeding continues, or if it stops and restarts within 24 hours after the first dose. The main analyses will be on an 'intention to treat' basis, irrespective of whether the allocated treatment was received or not. Subgroup analyses for the primary outcome will be based on type of delivery; administration or not of prophylactic uterotonics; and on whether the clinical decision to consider trial entry was based primarily on estimated blood loss alone or on haemodynamic instability. A study with 15,000 women will have over 90% power to detect a 25% reduction from 4% to 3% in the primary endpoint of mortality or hysterectomy.Trial registration
Current Controlled Trials: ISRCTN76912190 and Clinicaltrials.gov ID: NCT00872469 相似文献154.
Craven RA Hanrahan S Totty N Harnden P Stanley AJ Maher ER Harris AL Trimble WS Selby PJ Banks RE 《Proteomics》2006,6(13):3880-3893
The von Hippel Lindau (VHL) tumour suppressor gene, VHL, plays a central role in development of sporadic conventional renal cell carcinomas (RCCs). Studying VHL function may, therefore, increase understanding of the pathogenesis of RCC and identify markers/therapeutic targets. Comparison of 2-DE protein profiles of VHL-defective RCC cells (UMRC2) transfected with control vector or wild-type VHL showed differences in 30 proteins, including several novel changes. One of the findings confirmed by Western blotting was up-regulation of the mitochondrial protein ubiquinol cytochrome c reductase complex core protein 2 following VHL transfection, a change that was also observed in two other cell line backgrounds. A marked decrease in expression of this and several other mitochondrial proteins was demonstrated in RCC tissues and using VHL-transfectants, several were shown to exhibit VHL-dependent regulation. Thus, VHL may contribute to the decreased mitochondrial function seen in RCC. A form of septin 2 down-regulated following VHL transfection was also identified. Septin 2 was up-regulated in 12/16 RCCs, while alteration of the form present was also observed in 1/3 tumours analysed. Thus, increased expression of septin 2 is a common event in RCC and protein modification may also alter septin 2 function in a subset of tumours. 相似文献
155.
Lin Y Kwon T Polo J Zhu YF Coates S Crawford K Dong C Wininger M Hall J Selby M Coit D Medina-Selby A McCoin C Ng P Drane D Chien D Han J Vajdy M Houghton M 《Journal of virology》2008,82(15):7492-7503
Broad, multispecific CD4+ and CD8+ T-cell responses to the hepatitis C virus (HCV), as well as virus-cross-neutralizing antibodies, are associated with recovery from acute infection and may also be associated in chronic HCV patients with a favorable response to antiviral treatment. In order to recapitulate all of these responses in an ideal vaccine regimen, we have explored the use of recombinant HCV polypeptides combined with various Th1-type adjuvants and replication-defective alphaviral particles encoding HCV proteins in various prime/boost modalities in BALB/c mice. Defective chimeric alphaviral particles derived from the Sindbis and Venezuelan equine encephalitis viruses encoding either the HCV envelope glycoprotein gpE1/gpE2 heterodimer (E1E2) or nonstructural proteins 3, 4, and 5 (NS345) elicited strong CD8+ T-cell responses but low CD4+ T helper responses to these HCV gene products. In contrast, recombinant E1E2 glycoproteins adjuvanted with MF59 containing a CpG oligonucleotide elicited strong CD4+ T helper responses but no CD8+ T-cell responses. A recombinant NS345 polyprotein also stimulated strong CD4+ T helper responses but no CD8+ T-cell responses when adjuvanted with Iscomatrix containing CpG. Optimal elicitation of broad CD4+ and CD8+ T-cell responses to E1E2 and NS345 was obtained by first priming with Th1-adjuvanted proteins and then boosting with chimeric, defective alphaviruses expressing these HCV genes. In addition, this prime/boost regimen resulted in the induction of anti-E1E2 antibodies capable of cross-neutralizing heterologous HCV isolates in vitro. This vaccine formulation and regimen may therefore be optimal in humans for protection against this highly heterogeneous global pathogen. 相似文献
156.
Qiao J Kottke T Willmon C Galivo F Wongthida P Diaz RM Thompson J Ryno P Barber GN Chester J Selby P Harrington K Melcher A Vile RG 《Nature medicine》2008,14(1):37-44
In many common cancers, dissemination of secondary tumors via the lymph nodes poses the most significant threat to the affected individual. Metastatic cells often reach the lymph nodes by mimicking the molecular mechanisms used by hematopoietic cells to traffic to peripheral lymphoid organs. Therefore, we exploited naive T cell trafficking in order to chaperone an oncolytic virus to lymphoid organs harboring metastatic cells. Metastatic burden was initially reduced by viral oncolysis and was then eradicated, as tumor cell killing in the lymph node and spleen generated protective antitumor immunity. Lymph node purging of tumor cells was possible even in virus-immune mice. Adoptive transfer of normal T cells loaded with oncolytic virus into individuals with cancer would be technically easy to implement both to reduce the distribution of metastases and to vaccinate the affected individual in situ against micrometastatic disease. As such, this adoptive transfer could have a great therapeutic impact, in the adjuvant setting, on many different cancer types. 相似文献
157.
Hill KS Errington F Steele LP Merrick A Morgan R Selby PJ Georgopoulos NT O'Donnell DM Melcher AA 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(5):3108-3115
In vivo, dendritic cells (DC) are programmed to orchestrate innate and adaptive immunity in response to pathogen-derived "danger" signals. Under particular circumstances, DC can also be directly cytotoxic against tumor cells, potentially allowing them to release tumor associated Ags from dying cells and then prime antitumor immunity against them. In this study, we describe the innate characteristics of DC (OK-DC) generated in vitro after exposure of immature human myeloid-derived DC to OK432, a penicillin-inactivated and lyophilized preparation of Streptococcus pyrogenes. OK-DC produced proinflammatory cytokines, stimulated autologous T cell proliferation and IFN-gamma secretion, expressed CCR7, and migrated in response to MIP-3beta. Moreover, OK-DC displayed strong, specific cytotoxicity toward tumor cell targets. This cytotoxicity was associated with novel, OK432-induced up-regulation of CD40L on the cell surface of OK-DC, and was absolutely dependent on expression of CD40 on the tumor targets. These data demonstrate that maturation of human DC with OK432, an adjuvant suitable for clinical use, induces direct tumor cell killing by DC, and describes a novel CD40/CD40L-mediated mechanism for specific DC antitumor cytotoxicity. 相似文献
158.
159.
P B Selby 《Mutation research》1973,18(1):77-88
The specific-locus mutation frequency resulting from 300 R of acute X-irradiation has been determined for the germ cells present in male mice at 2, 4, 6, 8, 10, 14, 21, 28, and 35 days of age. The sample size was large enough for each of these nine age groups to ensure that a high mutation rate would be noticed. The testis of the mouse undergoes many developmental changes between birth, when most or all germ cells are gonocytes, and 35 days, when the cell population has come to resemble that of the adult. It was important to know if the germ cells present in these developmental stages of immature male mice yield the same mutation frequency as that found earlier for spermatogonia in the adult by W. L. Russell.None of the nine age groups has a mutation rate statistically significantly higher than that of the adult. Taken together, the nine groups of males have an average mutation frequency quite to that of the adult. This does not rule out the possibility that individual age groups may have a mutation frequency somewhat different from that of the adult.The distribution of mutations among the loci seems to be similar to that found for mutations induced in spermatogonia of the adult. Clusters of specific-locus mutations were found only on day 21.This paper and that presented earlier on the newborn report the first specific-locus mutation-rate studies on male mice irradiated between birth and adulthood. If the results can be carried over to man, it can be concluded that irradiation of the immature testis, from birth to puberty, will not present any greatly increased genetic hazard over that from irradiation of the adult testis. In fact, as the data stand in the mouse, they indicate a mutation rate similar to the adult for all but the earlier stages tested and, for these stages, a probably lower rate, representing a transition from the significantly lower rate reported earlier for newborns. 相似文献
160.
Selection of a Novel Anti-Nicotine Vaccine: Influence of Antigen Design on Antibody Function in Mice
David C. Pryde Lyn H. Jones David P. Gervais David R. Stead David C. Blakemore Matthew D. Selby Alan D. Brown Jotham W. Coe Matthew Badland David M. Beal Rebecca Glen Yvonne Wharton Gavin J. Miller Phil White Ningli Zhang Michelle Benoit Karen Robertson James R. Merson Heather L. Davis Michael J. McCluskie 《PloS one》2013,8(10)
Anti-nicotine vaccines may aid smoking cessation via the induction of anti-nicotine antibodies (Ab) which reduce nicotine entering the brain, and hence the associated reward. Ab function depends on both the quantity (titer) and the quality (affinity) of the Ab. Anti-nicotine vaccines tested previously in clinical studies had poor efficacy despite high Ab titer, and this may be due to inadequate function if Ab of low affinity were induced. In this study, we designed and synthesized a series of novel nicotine-like haptens which were all linked to diphtheria toxoid (DT) as carrier, but which differed in the site of attachment of linker to nicotine, the nature of linker used, and the handle used to attach the hapten to DT. The resulting hapten conjugates were evaluated in a mouse model, using CpG (a TLR9 agonist) and aluminum hydroxide (Al(OH)3) as adjuvants, whereby Ab titers, affinity and function were evaluated using a radiolabeled nicotine challenge model. A series of additional linkers varying in length, rigidity and polarity were used with a single hapten to generate additional DT-conjugates, which were also tested in mice. Conjugates made with different haptens resulted in various titers of anti-nicotine Ab. Several haptens gave similarly high Ab titers, but among these, Ab affinity and hence function varied considerably. Linker also influenced Ab titer, affinity and function. These results demonstrate that immune responses induced in mice by nicotine-conjugate antigens are greatly influenced by hapten design including site of attachment of linker to nicotine, the nature of linker used, and the handle used to attach the hapten to DT. While both Ab titer and affinity contributed to function, affinity was more sensitive to antigen differences. 相似文献