全文获取类型
收费全文 | 608篇 |
免费 | 47篇 |
国内免费 | 1篇 |
出版年
2021年 | 10篇 |
2019年 | 6篇 |
2018年 | 9篇 |
2017年 | 8篇 |
2016年 | 9篇 |
2015年 | 17篇 |
2014年 | 15篇 |
2013年 | 23篇 |
2012年 | 14篇 |
2011年 | 28篇 |
2010年 | 14篇 |
2009年 | 20篇 |
2008年 | 17篇 |
2007年 | 18篇 |
2006年 | 12篇 |
2005年 | 11篇 |
2004年 | 14篇 |
2003年 | 16篇 |
2002年 | 7篇 |
2001年 | 11篇 |
2000年 | 13篇 |
1999年 | 14篇 |
1998年 | 10篇 |
1997年 | 7篇 |
1996年 | 8篇 |
1994年 | 5篇 |
1992年 | 10篇 |
1991年 | 7篇 |
1990年 | 11篇 |
1989年 | 11篇 |
1988年 | 7篇 |
1987年 | 5篇 |
1986年 | 7篇 |
1985年 | 8篇 |
1984年 | 19篇 |
1983年 | 10篇 |
1982年 | 19篇 |
1981年 | 21篇 |
1980年 | 19篇 |
1979年 | 17篇 |
1978年 | 9篇 |
1977年 | 6篇 |
1976年 | 11篇 |
1975年 | 7篇 |
1974年 | 6篇 |
1973年 | 11篇 |
1972年 | 14篇 |
1970年 | 5篇 |
1968年 | 5篇 |
1938年 | 4篇 |
排序方式: 共有656条查询结果,搜索用时 15 毫秒
41.
42.
Scott Geibel Kassahun Habtamu Gebeyehu Mekonnen Nrupa Jani Lynnette Kay Julyata Shibru Lake Bedilu Samuel Kalibala 《PloS one》2016,11(2)
Objective
Evaluate the reliability and validity of the Youth Self-Report (YSR) as a screening tool for mental health problems among young people vulnerable to HIV in Ethiopia.Design
A cross-sectional assessment of young people currently receiving social services.Methods
Young people age 15–18 participated in a study where a translated and adapted version of the YSR was administered by trained nurses, followed by an assessment by Ethiopian psychiatrists. Internal reliability of YSR syndrome scales were assessed using Chronbach''s alpha. Test-retest reliability was assessed through repeating the YSR one month later. To assess validity, analysis of the sensitivity and specificity of the YSR compared to the psychiatrist assessment was conducted.Results
Across the eight syndrome scales, the YSR best measured the diagnosis of anxiety/depression and social problems among young women, and attention problems among young men. Among individual YSR syndrome scales, internal reliability ranged from unacceptable (Chronback’s alpha = 0.11, rule-breaking behavior among young women) to good (α≥0.71, anxiety/depression among young women). Anxiety/depression scores of ≥8.5 among young women also had good sensitivity (0.833) and specificity (0.754) to predict a true diagnosis. The YSR syndrome scales for social problems among young women and attention problems among young men also had fair consistency and validity measurements. Most YSR scores had significant positive correlations between baseline and post-one month administration. Measures of reliability and validity for most other YSR syndrome scales were fair to poor.Conclusions
The adapted, personally administered, Amharic version of the YSR has sufficient reliability and validity in identifying young vulnerable women with anxiety/depression and/or social problems, and young men with attention problems; which were the most common mental health disorders observed by psychiatrists among the migrant populations in this study. Further assessment of the applicability of the YSR among vulnerable young people for less common disorders in Ethiopia is needed. 相似文献43.
Nihal Kenawy Helen Kalirai Joseph J. Sacco Sarah L. Lake Steffen Heegaard Ann‐Cathrine Larsen Paul T. Finger Tatyana Milman Kimberly Chin Carlo Mosci Francesco Lanza Alexandre Moulin Caroline A. Schmitt Jean Pierre Caujolle Clia Maschi Marina Marinkovic Azzam F. Taktak Heinrich Heimann Bertil E. Damato Sarah E. Coupland 《Pigment cell & melanoma research》2019,32(4):564-575
Relatively little is known about the genetic aberrations of conjunctival melanomas (CoM) and their correlation with clinical and histomorphological features as well as prognosis. The aim of this large collaborative multicenter study was to determine potential key biomarkers for metastatic risk and any druggable targets for high metastatic risk CoM. Using Affymetrix single nucleotide polymorphism genotyping arrays on 59 CoM, we detected frequent amplifications on chromosome (chr) 6p and deletions on 7q, and characterized mutation‐specific copy number alterations. Deletions on chr 10q11.21‐26.2, a region harboring the tumor suppressor genes, PDCD4, SUFU, NEURL1, PTEN, RASSF4, DMBT1, and C10orf90 and C10orf99, significantly correlated with metastasis (Fisher's exact, p ≤ 0.04), lymphatic invasion (Fisher's exact, p ≤ 0.02), increasing tumor thickness (Mann–Whitney, p ≤ 0.02), and BRAF mutation (Fisher's exact, p ≤ 0.05). This enhanced insight into CoM biology is a step toward identifying patients at risk of metastasis and potential therapeutic targets for systemic disease. 相似文献
44.
CD8+ T-lymphocytes recognize peptides in the context of major histocompatibility complex (MHC) class I antigens. Upon activation, these cells differentiate into effector cytotoxic T lymphocytes (CTL) and no longer require formal antigen presentation by professional antigen presenting cells (APC). Subsequently, any cell expressing MHC class I/cognate peptide can stimulate CTL. Using TIL specific for a melanoma antigen-derived peptide, IMDQVPFSV (g209 2M), we sought to determine whether these CTL could present peptide to each other. Our findings demonstrate that peptide presentation of the g209 2M peptide epitope by TIL is comparable to conventional methods of using T2 cells as APC. We report here that CTL are capable of self-presentation of antigenic peptide to neighboring CTL resulting in IFN-gamma secretion, proliferation, and lysis of peptide-loaded CTL. These results demonstrate that human TIL possess both APC functions as well as cytotoxic functions and that this phenomenon could influence CTL activity elicited by immunotherapy. 相似文献
45.
Class II multimer formation is an important event in immune recognition. Not only is multimerization a prerequisite for T cell activation, but it is a signal to APC. In the present article, we propose that multimerization can result in the specific removal of ligand complexes from the cell surface of the APC, an event which may influence the overall pattern of T cell reactivity. 相似文献
46.
The development of technology to measure antigen presentation in the secondary lymphoid system has provided the opportunity of analysing components of the host antitumour immune response that have, until now, been unavailable for study. In particular, this technology has enabled us to evaluate threshold levels of tumour antigen required for cross-presentation in draining lymph nodes, the duration of this antigen presentation and processes that regulate tumour antigen presentation. Thus, we have been able to dissect out the relationship between antigen presentation and the resultant development of effector function in class I-restricted T cells, as well as the role of regulatory CD4 cells. We have also used this technology to evaluate the effects of antitumour therapy on local antigen cross-presentation. 相似文献
47.
In this study precision-cut liver slices have been used to evaluate the effects of the flavone tangeretin, the flavonoid glycoside naringin and the flavanone naringenin (the aglycone derived from naringin) on xenobiotic-induced genotoxicity. Liver slices were cultured for 24 h in medium containing [3H]thymidine and the test compounds and then processed for autoradiographic determination of unscheduled DNA synthesis (UDS). The cooked food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) markedly induced UDS in cultured human liver slices and both 2-acetylaminofluorene (2-AAF) and aflatoxin B1 (AFB1) induced UDS in cultured rat liver slices. Tangeretin (20 and 50 microM) was found to be a potent inhibitor of 5 and 50 microM PhIP-induced UDS in human liver slices, whereas 20 and 50 microM naringenin was ineffective and naringin only inhibited genotoxicity at a concentration of 1000 microM. In rat liver slices 50 microM tangeretin inhibited 10 and 50 microM 2-AAF-induced UDS, whereas 50 microM naringenin and 100 and 1000 microM naringin were ineffective. None of the three flavonoids examined inhibited 5 microM AFB1-induced UDS in rat liver slices. The inhibition of PhIP- and 2-AAF-induced UDS by tangeretin is probably attributable to the inhibition of the human and rat cytochrome P-450 isoforms which are responsible for the bioactivation of these two genotoxins. Although flavonoids can modulate xenobiotic-induced genotoxicity in human and rat liver slices, any protective effect is dependent on the particular combination of genotoxin and flavonoid examined. These results demonstrate that cultured precision-cut liver slices may be utilised as an in vitro model system to examine the modulation of xenobiotic-induced genotoxicity by flavonoids and other dietary components. 相似文献
48.
In this study, four modified gp100 peptides were designed by combining amino acids from the melanoma peptide antigen gp100((209-217)) with preferred primary and auxiliary HLA-A *0201 anchor residues previously identified from combinatorial peptide library screening with recombinant HLA-A*0201. These modified peptides demonstrated stronger binding affinity for the HLA-A*0201 molecule compared to wild-type gp100 peptide. Nine CTL lines generated from patients immunized with the g209-2 M peptide and one CTL line from a non-immunized patient were tested for the ability to respond to these modified gp100 peptides. Stimulation of CTL by two of four modified peptides induced higher levels of IFN-gamma secretion than the wild-type gp100 peptide, demonstrating that higher peptide binding affinity for HLA molecules does not necessarily equate to functional activity of CTL. Two major and one minor CTL recognition pattern were observed, irrespective of previous peptide immunization, suggesting that multiple, rationally designed modified tumor peptides for the same epitope stimulate a broad CTL response by activating multiple CTL capable of cross-reacting with the natural antigenic peptide. 相似文献
49.
Induction of tumor cell apoptosis in vivo increases tumor antigen cross-presentation,cross-priming rather than cross-tolerizing host tumor-specific CD8 T cells 总被引:14,自引:0,他引:14
Nowak AK Lake RA Marzo AL Scott B Heath WR Collins EJ Frelinger JA Robinson BW 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(10):4905-4913
Cross-presentation of cell-bound Ags from established, solid tumors to CD8 cells is efficient and likely to have a role in determining host response to tumor. A number of investigators have predicted that when tumor Ags are derived from apoptotic cells either no response, due to Ag "sequestration," or CD8 cross-tolerance would ensue. Because the crucial issue of whether this happens in vivo has never been addressed, we induced apoptosis of established hemagglutinin (HA)-transfected AB1 tumors in BALB/c mice using the apoptosis-inducing reagent gemcitabine. This shrank the tumor by approximately 80%. This induction of apoptosis increased cross-presentation of HA to CD8 cells yet neither gross deletion nor functional tolerance of HA-specific CD8 cells were observed, based on tetramer analysis, proliferation of specific CD8 T cells, and in vivo CTL activity. Interestingly, apoptosis primed the host for a strong antitumor response to a second, virus-generated HA-specific signal in that administration of an HA-expressing virus after gemcitabine administration markedly decreased tumor growth compared with viral administration without gemcitabine. Thus tumor cell apoptosis in vivo neither sequesters tumor Ags nor cross-tolerizes tumor-specific CD8 cells. This observation has fundamental consequences for the development of tumor immunotherapy protocols and for understanding T cell reactivity to tumors and the in vivo immune responses to apoptotic cells. 相似文献
50.