全文获取类型
收费全文 | 524篇 |
免费 | 51篇 |
出版年
2021年 | 5篇 |
2020年 | 6篇 |
2019年 | 6篇 |
2017年 | 5篇 |
2016年 | 14篇 |
2015年 | 14篇 |
2014年 | 17篇 |
2013年 | 22篇 |
2012年 | 30篇 |
2011年 | 29篇 |
2010年 | 21篇 |
2009年 | 13篇 |
2008年 | 23篇 |
2007年 | 31篇 |
2006年 | 28篇 |
2005年 | 24篇 |
2004年 | 15篇 |
2003年 | 33篇 |
2002年 | 31篇 |
2001年 | 9篇 |
2000年 | 6篇 |
1999年 | 11篇 |
1998年 | 4篇 |
1997年 | 7篇 |
1996年 | 7篇 |
1995年 | 8篇 |
1994年 | 8篇 |
1993年 | 5篇 |
1992年 | 5篇 |
1991年 | 7篇 |
1990年 | 7篇 |
1989年 | 6篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 3篇 |
1984年 | 6篇 |
1983年 | 7篇 |
1982年 | 8篇 |
1980年 | 5篇 |
1977年 | 3篇 |
1976年 | 6篇 |
1974年 | 7篇 |
1973年 | 3篇 |
1970年 | 3篇 |
1968年 | 7篇 |
1967年 | 6篇 |
1963年 | 5篇 |
1958年 | 3篇 |
1935年 | 3篇 |
1928年 | 4篇 |
排序方式: 共有575条查询结果,搜索用时 375 毫秒
81.
Antonia Sophie Wenners Keyur Mehta Sibylle Loibl Hyerim Park Berit Mueller Norbert Arnold Sigrid Hamann Joerg Weimer Beyhan Ataseven Silvia Darb-Esfahani Christian Schem Christoph Mundhenke Fariba Khandan Christoph Thomssen Walter Jonat Hans-Juergen Holzhausen Gunther von Minckwitz Carsten Denkert Maret Bauer 《PloS one》2012,7(10)
In our previous work we showed that NGAL, a protein involved in the regulation of proliferation and differentiation, is overexpressed in human breast cancer (BC) and predicts poor prognosis. In neoadjuvant chemotherapy (NACT) pathological complete response (pCR) is a predictor for outcome. The aim of this study was to evaluate NGAL as a predictor of response to NACT and to validate NGAL as a prognostic factor for clinical outcome in patients with primary BC. Immunohistochemistry was performed on tissue microarrays from 652 core biopsies from BC patients, who underwent NACT in the GeparTrio trial. NGAL expression and intensity was evaluated separately. NGAL was detected in 42.2% of the breast carcinomas in the cytoplasm. NGAL expression correlated with negative hormone receptor (HR) status, but not with other baseline parameters. NGAL expression did not correlate with pCR in the full population, however, NGAL expression and staining intensity were significantly associated with higher pCR rates in patients with positive HR status. In addition, strong NGAL expression correlated with higher pCR rates in node negative patients, patients with histological grade 1 or 2 tumors and a tumor size <40 mm. In univariate survival analysis, positive NGAL expression and strong staining intensity correlated with decreased disease-free survival (DFS) in the entire cohort and different subgroups, including HR positive patients. Similar correlations were found for intense staining and decreased overall survival (OS). In multivariate analysis, NGAL expression remained an independent prognostic factor for DFS. The results show that in low-risk subgroups, NGAL was found to be a predictive marker for pCR after NACT. Furthermore, NGAL could be validated as an independent prognostic factor for decreased DFS in primary human BC. 相似文献
82.
We present a multiview selective-plane illumination microscope (MuVi-SPIM), comprising two detection and illumination objective lenses, that allows rapid in toto fluorescence imaging of biological specimens with subcellular resolution. The fixed geometrical arrangement of the imaging branches enables multiview data fusion in real time. The high speed of MuVi-SPIM allows faithful tracking of nuclei and cell shape changes, which we demonstrate through in toto imaging of the embryonic development of Drosophila melanogaster. 相似文献
83.
Gunther Doehlemann Ramon Wahl Miroslav Vranes Ronald P. de Vries Jrg Kmper Regine Kahmann 《Journal of plant physiology》2008,165(1):29
The fungus Ustilago maydis is a biotrophic pathogen parasitizing on maize. The most prominent symptoms of the disease are large tumors in which fungal proliferation and spore differentiation occur. In this study, we have analyzed early and late tumor stages by confocal microscopy. We show that fungal differentiation occurs both within plant cells as well as in cavities where huge aggregates of fungal mycelium develop. U. maydis is poorly equipped with plant CWDEs and we demonstrate by array analysis that the respective genes follow distinct expression profiles at early and late stages of tumor development. For the set of three genes coding for pectinolytic enzymes, deletion mutants were generated by gene replacement. Neither single nor triple mutants were affected in pathogenic development. Based on our studies, we consider it unlikely that U. maydis feeds on carbohydrates derived from the digestion of plant cell wall material, but uses its set of plant CWDEs for softening the cell wall structure as a prerequisite for in planta growth. 相似文献
84.
Markus Gusset Anthony H. Maddock Glenn J. Gunther Micaela Szykman Rob Slotow Michele Walters Michael J. Somers 《Biodiversity and Conservation》2008,17(1):83-101
In South Africa, a plan was launched to manage separate sub-populations of endangered African wild dogs (Lycaon pictus) in several small, geographically isolated, conservation areas as a single meta-population. This intensive management approach
involves the re-introduction of wild dogs into suitable conservation areas and periodic translocations among them. To assess
the attitudes towards re-introduced wild dogs, we conducted a questionnaire survey of multiple stakeholders—local community
members, private landowners and tourists—in and around Hluhluwe-iMfolozi Park (HiP), one of the meta-population conservation
areas. Here, we document conflicting human interests over the re-introduced wild dogs. Tourists in HiP, on the one hand, expressed
overwhelmingly positive opinions about wild dogs across personal details of the respondents, but especially after having seen
free-ranging wild dogs. On the other hand, we found misconceptions and perceptions that were more negative among the rural
population around HiP, again largely independent of personal details of the participants, although educated respondents voiced
more favourable views of wild dogs. These negative attitudes were in particular due to perceived and real threats of livestock
losses. In a follow-up questionnaire survey, we also discovered apparent shortcomings of a previous short-lived conservation
education programme among the local communities adjacent to HiP. Consequently, the mitigation of the conflict between wild
dogs and rural people requires an understanding of the conditions under which livestock predation occurs, the encouragement
of practices that prevent such predation, and increasing local tolerance of co-existence with wild dogs through both economic
and non-monetary incentive schemes as well as continued conservation education. 相似文献
85.
Doehlemann G Wahl R Horst RJ Voll LM Usadel B Poree F Stitt M Pons-Kühnemann J Sonnewald U Kahmann R Kämper J 《The Plant journal : for cell and molecular biology》2008,56(2):181-195
The fungal pathogen Ustilago maydis establishes a biotrophic relationship with its host plant maize (Zea mays). Hallmarks of the disease are large plant tumours in which fungal proliferation occurs. Previous studies suggested that classical defence pathways are not activated. Confocal microscopy, global expression profiling and metabolic profiling now shows that U. maydis is recognized early and triggers defence responses. Many of these early response genes are downregulated at later time points, whereas several genes associated with suppression of cell death are induced. The interplay between fungus and host involves changes in hormone signalling, induction of antioxidant and secondary metabolism, as well as the prevention of source leaf establishment. Our data provide novel insights into the complexity of a biotrophic interaction. 相似文献
86.
Hepatitis C Virus Genotype 1b Core Protein Does Not Exert Immunomodulatory Effects on Virus-Induced Cellular Immunity 总被引:3,自引:0,他引:3
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Zhang-Xu Liu Hiroshi Nishida Jian-Wen He Michael M. C. Lai Ni Feng Gunther Dennert 《Journal of virology》2002,76(3):990-997
The hepatitis C virus (HCV) core protein is among the most conserved proteins in HCV and is known to induce sensitization of cytotoxic T lymphocytes (CTL). Therefore, it is a prime candidate for a component of a potential HCV vaccine. The HCV core protein has, however, been reported to exert multiple effects on cell functions, raising questions as to its suitability for this purpose. This question was investigated here with mice into which replication-deficient adenoviruses expressing core protein of an HCV genotype 1b isolate were injected. We show that induction of cytokines in response to the infection, infiltration of lymphocytes into the infected liver, priming of virus-specific CTL, and liver injury are not modulated by expression of the core protein in the liver. Moreover, no changes in the sensitivity to tumor necrosis factor alpha- or Fas-mediated liver injury are demonstrable. A similar lack of demonstrable effects of the core protein on immune functions has also been obtained using transgenic mice expressing another HCV genotype 1b core protein. It is concluded that the HCV core protein of genotype 1b has no modulatory effects on induction of virus-specific immune responses and may therefore be a suitable component of an HCV vaccine. 相似文献
87.
Respiratory Syncytial Virus Fusion Protein Mediates Inhibition of Mitogen-Induced T-Cell Proliferation by Contact
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Jrg Schlender Gunther Walliser Jens Fricke Karl-Klaus Conzelmann 《Journal of virology》2002,76(3):1163-1170
Human respiratory syncytial virus (HRSV) and bovine respiratory syncytial virus (BRSV) are major pathogens in infants and calves, respectively. Experimental BRSV infection of calves and lambs is associated with lymphopenia and a reduction in responsiveness of peripheral blood lymphocytes (PBLs) to mitogens ex vivo. In this report, we show that in vitro mitogen-induced proliferation of PBLs is inhibited after contact with RSV-infected and UV-inactivated cells or with cells expressing RSV envelope proteins on the cell surface. The protein responsible was identified as the RSV fusion protein (F), as cells infected with a recombinant RSV expressing F as the single envelope protein or cells transfected with a plasmid encoding F were able to induce this effect. Thus, direct contact with RSV F is necessary and sufficient to inhibit proliferation of PBLs. Interestingly, F derived from HRSV was more efficient in inhibiting human PBL proliferation, while F from BRSV was more efficient in inhibiting bovine PBLs. Since various T-cell activation markers were upregulated after presenter cell contact, T lymphocytes are viable and may still be activated by mitogen. However, a significant fraction of PBLs were delayed or defective in G0/G1 to S-phase transit. 相似文献
88.
Butyrate reversibly arrests the proliferation of normal and Rous sarcoma virus-infected chicken heart mesenchymal cells 总被引:3,自引:0,他引:3
Sodium butyrate at 5 X 10(-3) M reversibly arrests the proliferation of both normal and RSV-infected chicken heart mesenchymal cells. This finding suggests that butyrate acts by causing non-specific inhibition of cell proliferation, rather then by specifically suppressing the neoplastic phenotype or by inducing recovery of cells from the neoplastic state. 相似文献
89.
90.
Chris Bowler Hanns Frohnmeyer Eberhard Schäfer Gunther Neuhaus Nam-Hai Chua 《Acta Physiologiae Plantarum》1997,19(4):475-483
The phytochromes are the best studied plant photoreceptors, controlling a wide variety of responses at both whole plant and
single cell levels. Three signal transduction pathways, dependent on cGMP and/or calcium, have been found to be utilized by
phytochrome to control the expression of genes required for chloroplast development (e.g., CAB and FNR) and anthocyanin biosynthesis (e.g., CHS). In particular, cGMP is a second messenger positively regulating CHS gene expression whilst calcium and calmodulin act as negative regulators. In addition to phytochrome regulation of CHS we have begun to examine the signal transduction pathways utilized by UV photoreceptors. In contrast to phytochrome-mediated
responses, results indicate a role for calcium and calmodulin as positive regulators of CHS gene expression in UV light. 相似文献