全文获取类型
收费全文 | 1000篇 |
免费 | 77篇 |
出版年
2023年 | 9篇 |
2022年 | 10篇 |
2021年 | 20篇 |
2020年 | 17篇 |
2019年 | 15篇 |
2018年 | 31篇 |
2017年 | 15篇 |
2016年 | 29篇 |
2015年 | 52篇 |
2014年 | 60篇 |
2013年 | 94篇 |
2012年 | 76篇 |
2011年 | 67篇 |
2010年 | 47篇 |
2009年 | 19篇 |
2008年 | 33篇 |
2007年 | 48篇 |
2006年 | 35篇 |
2005年 | 36篇 |
2004年 | 43篇 |
2003年 | 30篇 |
2002年 | 36篇 |
2001年 | 18篇 |
2000年 | 16篇 |
1999年 | 13篇 |
1998年 | 13篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 5篇 |
1993年 | 7篇 |
1992年 | 11篇 |
1991年 | 16篇 |
1990年 | 7篇 |
1989年 | 7篇 |
1988年 | 9篇 |
1987年 | 8篇 |
1986年 | 12篇 |
1985年 | 13篇 |
1984年 | 10篇 |
1983年 | 5篇 |
1979年 | 7篇 |
1976年 | 7篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1970年 | 4篇 |
1968年 | 6篇 |
1967年 | 5篇 |
1966年 | 4篇 |
排序方式: 共有1077条查询结果,搜索用时 234 毫秒
81.
Covalent modifier NEDD8 is essential for SCF ubiquitin-ligase in fission yeast 总被引:6,自引:0,他引:6
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Osaka F Saeki M Katayama S Aida N Toh-E A Kominami K Toda T Suzuki T Chiba T Tanaka K Kato S 《The EMBO journal》2000,19(13):3475-3484
A ubiquitin-like modifier, NEDD8, is covalently attached to cullin-family proteins, but its physiological role is poorly understood. Here we report that the NEDD8-modifying pathway is essential for cell viability and function of Pcu1 (cullin-1 orthologue) in fission yeast. Pcu1 assembled on SCF ubiquitin-ligase was completely modified by NEDD8. Pcu1(K713R) defective for NEDD8 conjugation lost the ability to complement lethality due to pcu1 deletion. Forced expression of Pcu1(K713R) or depletion of NEDD8 in cells resulted in impaired cell proliferation and marked stabilization of the cyclin-dependent kinase inhibitor Rum1, which is a substrate of the SCF complex. Based on these findings, we propose that covalent modification of cullin-1 by the NEDD8 system plays an essential role in the function of SCF in fission yeast. 相似文献
82.
83.
Posttranscriptional stimulation of endothelial cell matrix metalloproteinases 2 and 1 by endothelioma cells 总被引:7,自引:0,他引:7
84.
Scott Dryden-Peterson Kara Bennett Michael D. Hughes Adrian Veres Oaitse John Rosina Pradhananga Matthew Boyer Carolyn Brown Bright Sakyi Erik van Widenfelt Koona Keapoletswe Madisa Mine Sikhulile Moyo Aida Asmelash Mark Siedner Mompati Mmalane Roger L. Shapiro Shahin Lockman 《PloS one》2015,10(2)
BackgroundLess than one-third of HIV-infected pregnant women eligible for combination antiretroviral therapy (ART) globally initiate treatment prior to delivery, with lack of access to timely CD4 results being a principal barrier. We evaluated the effectiveness of an SMS-based intervention to improve access to timely antenatal ART.MethodsWe conducted a stepped-wedge cluster randomized trial of a low-cost programmatic intervention in 20 antenatal clinics in Gaborone, Botswana. From July 2011-April 2012, 2 clinics were randomly selected every 4 weeks to receive an ongoing clinic-based educational intervention to improve CD4 collection and to receive CD4 results via an automated SMS platform with active patient tracing. CD4 testing before 26 weeks gestation and ART initiation before 30 weeks gestation were assessed.ResultsThree-hundred-sixty-six ART-naïve women were included, 189 registering for antenatal care under Intervention and 177 under Usual Care periods. Of CD4-eligible women, 100 (59.2%) women under Intervention and 79 (50.6%) women under Usual Care completed CD4 phlebotomy before 26 weeks gestation, adjusted odds ratio (aOR, adjusted for time that a clinic initiated Intervention) 0.87 (95% confidence interval [CI]0.47–1.63, P = 0.67). The SMS-based platform reduced time to clinic receipt of CD4 test result from median of 16 to 6 days (P<0.001), was appreciated by clinic staff, and was associated with reduced operational cost. However, rates of ART initiation remained low, with 56 (36.4%) women registering under Intervention versus 37 (24.2%) women under Usual Care initiating ART prior to 30 weeks gestation, aOR 1.06 (95%CI 0.53–2.13, P = 0.87).ConclusionsThe augmented SMS-based intervention delivered CD4 results more rapidly and efficiently, and this type of SMS-based results delivery platform may be useful for a variety of tests and settings. However, the intervention did not appear to improve access to timely antenatal CD4 testing or ART initiation, as obstacles other than CD4 impeded ART initiation during pregnancy. 相似文献
85.
Thrombospondin‐1 is part of a Slug‐independent motility and metastatic program in cutaneous melanoma,in association with VEGFR‐1 and FGF‐2
下载免费PDF全文
![点击此处可从《Pigment cell & melanoma research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Patrizia Borsotti Carmen Ghilardi Paola Ostano Antonietta Silini Romina Dossi Denise Pinessi Chiara Foglieni Maria Scatolini Pedro M. Lacal Raffaele Ferrari Davide Moscatelli Fabio Sangalli Stefania D'Atri Raffaella Giavazzi Maria Rosa Bani Giovanna Chiorino Giulia Taraboletti 《Pigment cell & melanoma research》2015,28(1):73-81
Differently from most transformed cells, cutaneous melanoma expresses the pleiotropic factor thrombospondin‐1 (TSP‐1). Herein, we show that TSP‐1 (RNA and protein), undetectable in four cultures of melanocytes and a RGP melanoma, was variously present in 13 cell lines from advanced melanomas or metastases. Moreover, microarray analysis of 55 human lesions showed higher TSP‐1 expression in primary melanomas and metastases than in common and dysplastic nevi. In a functional enrichment analysis, the expression of TSP‐1 correlated with motility‐related genes. Accordingly, TSP‐1 production was associated with melanoma cell motility in vitro and lung colonization potential in vivo. VEGF/VEGFR‐1 and FGF‐2, involved in melanoma progression, regulated TSP‐1 production. These factors were coexpressed with TSP‐1 and correlated negatively with Slug (SNAI2), a cell migration master gene implicated in melanoma metastasis. We conclude that TSP‐1 cooperates with FGF‐2 and VEGF/VEGFR‐1 in determining melanoma invasion and metastasis, as part of a Slug‐independent motility program. 相似文献
86.
87.
Elie A. Akl Fadi El-Jardali Lama Bou Karroum Jamale El-Eid Hneine Brax Chaza Akik Mona Osman Ghayda Hassan Mira Itani Aida Farha Kevin Pottie Sandy Oliver 《PloS one》2015,10(9)
Background
Effective coordination between organizations, agencies and bodies providing or financing health services in humanitarian crises is required to ensure efficiency of services, avoid duplication, and improve equity. The objective of this review was to assess how, during and after humanitarian crises, different mechanisms and models of coordination between organizations, agencies and bodies providing or financing health services compare in terms of access to health services and health outcomes.Methods
We registered a protocol for this review in PROSPERO International prospective register of systematic reviews under number PROSPERO2014:CRD42014009267. Eligible studies included randomized and nonrandomized designs, process evaluations and qualitative methods. We electronically searched Medline, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, and the WHO Global Health Library and websites of relevant organizations. We followed standard systematic review methodology for the selection, data abstraction, and risk of bias assessment. We assessed the quality of evidence using the GRADE approach.Results
Of 14,309 identified citations from databases and organizations'' websites, we identified four eligible studies. Two studies used mixed-methods, one used quantitative methods, and one used qualitative methods. The available evidence suggests that information coordination between bodies providing health services in humanitarian crises settings may be effective in improving health systems inputs. There is additional evidence suggesting that management/directive coordination such as the cluster model may improve health system inputs in addition to access to health services. None of the included studies assessed coordination through common representation and framework coordination. The evidence was judged to be of very low quality.Conclusion
This systematic review provides evidence of possible effectiveness of information coordination and management/directive coordination between organizations, agencies and bodies providing or financing health services in humanitarian crises. Our findings can inform the research agenda and highlight the need for improving conduct and reporting of research in this field. 相似文献88.
Maj Rabjerg Aida Oliván-Viguera Lars Koch Hansen Line Jensen Linda Sevelsted-M?ller Steen Walter Boye L. Jensen Niels Marcussen Ralf K?hler 《PloS one》2015,10(4)
Background
Ca2+-activated K+ channels have been implicated in cancer cell growth, metastasis, and tumor angiogenesis. Here we hypothesized that high mRNA and protein expression of the intermediate-conductance Ca2+-activated K+ channel, KCa3.1, is a molecular marker of clear cell Renal Cell Carcinoma (ccRCC) and metastatic potential and survival.Methodology/Principal Findings
We analyzed channel expression by qRT-PCR, immunohistochemistry, and patch-clamp in ccRCC and benign oncocytoma specimens, in primary ccRCC and oncocytoma cell lines, as well as in two ccRCC cell lines (Caki-1 and Caki-2). CcRCC specimens contained 12-fold higher mRNA levels of KCa3.1 than oncocytoma specimens. The large-conductance channel, KCa1.1, was 3-fold more highly expressed in ccRCC than in oncocytoma. KCa3.1 mRNA expression in ccRCC was 2-fold higher than in the healthy cortex of the same kidney. Disease specific survival trended towards reduction in the subgroup of high-KCa3.1-expressing tumors (p<0.08 vs. low-KCa3.1-expressing tumors). Progression-free survival (time to metastasis/recurrence) was reduced significantly in the subgroup of high-KCa3.1-expressing tumors (p<0.02, vs. low-KCa3.1-expressing tumors). Immunohistochemistry revealed high protein expression of KCa3.1 in tumor vessels of ccRCC and oncocytoma and in a subset of ccRCC cells. Oncocytoma cells were devoid of KCa3.1 protein. In a primary ccRCC cell line and Caki-1/2-ccRCC cells, we found KCa3.1-protein as well as TRAM-34-sensitive KCa3.1-currents in a subset of cells. Furthermore, Caki-1/2-ccRCC cells displayed functional Paxilline-sensitive KCa1.1 currents. Neither KCa3.1 nor KCa1.1 were found in a primary oncocytoma cell line. Yet KCa-blockers, like TRAM-34 (KCa3.1) and Paxilline (KCa1.1), had no appreciable effects on Caki-1 proliferation in-vitro.Conclusions/Significance
Our study demonstrated expression of KCa3.1 in ccRCC but not in benign oncocytoma. Moreover, high KCa3.1-mRNA expression levels were indicative of low disease specific survival of ccRCC patients, short progression-free survival, and a high metastatic potential. Therefore, KCa3.1 is of prognostic value in ccRCC. 相似文献89.
90.
Tereza Pilar-Fonseca João Pereira Aida Campos Ana Moreno Paulo Fonseca Manuel Afonso-Dias 《Hydrobiologia》2014,725(1):137-144
This study presents a 1-year synopsis of the trawl fishery for the European squid Loligo vulgaris in Portuguese waters, integrating length-structured landings with corresponding geo-referenced fishing activities. From vessel monitoring system (VMS) data, landings and biological sampling, a “status-report” was obtained for 2003. Fishing pressure was found to be most intense in inshore areas of the northwest and the south coasts. Population size structure, classified into three categories, was not uniform throughout the fishing areas. Larger squid are found offshore in the northwest (International Council for the Exploration of the Sea—ICES rectangle 10E0) and in the south (rectangles 2E1 and 3E1), whereas all inshore western coast rectangles showed larger proportions of small squid relative to the southern rectangles. The analysis carried out in this study provides an insight into the possible impact of the fishing intensity pattern on the population structure in various zones. The results demonstrate the benefits of combining geo-referenced fisheries information with landings and size data, to produce explicit spatio-temporal information that can contribute to integrated planning and management for the sustainable exploitation of this resource. 相似文献