全文获取类型
收费全文 | 910篇 |
免费 | 61篇 |
专业分类
971篇 |
出版年
2023年 | 3篇 |
2022年 | 20篇 |
2021年 | 28篇 |
2020年 | 13篇 |
2019年 | 14篇 |
2018年 | 23篇 |
2017年 | 24篇 |
2016年 | 29篇 |
2015年 | 52篇 |
2014年 | 58篇 |
2013年 | 83篇 |
2012年 | 69篇 |
2011年 | 65篇 |
2010年 | 51篇 |
2009年 | 41篇 |
2008年 | 50篇 |
2007年 | 66篇 |
2006年 | 61篇 |
2005年 | 51篇 |
2004年 | 26篇 |
2003年 | 35篇 |
2002年 | 33篇 |
2001年 | 7篇 |
2000年 | 3篇 |
1999年 | 7篇 |
1998年 | 8篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 6篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有971条查询结果,搜索用时 15 毫秒
11.
De Luca A Gallo M Aldinucci D Ribatti D Lamura L D'Alessio A De Filippi R Pinto A Normanno N 《Journal of cellular physiology》2011,226(8):2131-2138
Increasing evidence suggests that bone marrow-derived mesenchymal stem cells (MSCs) are recruited into the stroma of developing tumors where they contribute to cancer progression. MSCs produce different growth factors that sustain tumor-associated neo-angiogenesis. Since the majority of carcinomas secrete ligands of the epidermal growth factor receptor (EGFR), we assessed the role of EGFR signaling in regulating the release of angiogenic factors in MSCs. Treatment of human primary MSCs and of the human osteoblastic cell line hFOB with transforming growth factor α (TGF-α), one of the main ligands of the EGFR, significantly induced activation of this receptor and of different intracellular signaling proteins, including the PI3K/AKT and the MEK/MAPK pathways. TGF-α induced a significant increase in the levels of secretion of vascular endothelial growth factor in both MSCs and hFOB. Conditioned medium from TGF-α treated MSCs showed an higher in vivo angiogenic effect as compared with medium from untreated cells. Treatment of MSCs with TGF-α also produced a significant increase in the secretion of other angiogenic growth factors such as angiopoietin-2, granulocyte-colony stimulating factor, hepatocyte growth factor, interleukin (IL)-6, IL-8, and platelet-derived growth factor-BB. Using selective MEK and PI3K inhibitors, we found that both MEK/MAPK and the PI3K/AKT signaling pathways mediate the ability of TGF-α to induce secretion of angiogenic factors in MSCs. Finally, stimulation with TGF-α increased the ability of MSCs to induce migration of MCF-7 breast cancer cells. These data suggest that EGFR signaling regulates the ability of MSCs to sustain cancer progression through the release of growth factors that promote neo-angiogenesis and tumor cell migration. 相似文献
12.
Santos CA Beloti LL Toledo MA Crucello A Favaro MT Mendes JS Santiago AS Azzoni AR Souza AP 《Protein expression and purification》2012,82(2):284-289
Xylella fastidiosa is a Gram-negative xylem-limited plant pathogenic bacterium responsible for several economically important crop diseases. Here, we present a novel and efficient protein refolding protocol for the solubilization and purification of recombinant X. fastidiosa peptidoglycan-associated lipoprotein (XfPal). Pal is an outer membrane protein that plays important roles in maintaining the integrity of the cell envelope and in bacterial pathogenicity. Because Pal has a highly hydrophobic N-terminal domain, the heterologous expression studies necessary for structural and functional protein characterization are laborious once the recombinant protein is present in inclusion bodies. Our protocol based on the denaturation of the XfPal-enriched inclusion bodies with 8M urea followed by buffer-exchange steps via dialysis proved effective for the solubilization and subsequent purification of XfPal, allowing us to obtain a large amount of relatively pure and folded protein. In addition, XfPal was biochemically and functionally characterized. The method for purification reported herein is valuable for further research on the three-dimensional structure and function of Pal and other outer membrane proteins and can contribute to a better understanding of the role of these proteins in bacterial pathogenicity, especially with regard to the plant pathogen X. fastidiosa. 相似文献
13.
Alessia Visconti Simone Ribero Marianna Sanna Tim D. Spector Veronique Bataille Mario Falchi 《Pigment cell & melanoma research》2020,33(2):326-333
Body site is highly relevant for melanoma: it affects prognosis and varies according to the patient's sex. The distribution of naevi, a major risk factor for melanoma, at different body sites also varies according to sex in childhood. Using naevus counts at different body sites in 492 unrelated adults from both sexes, we observed that women have an increased number of naevi on the lower limbs compared to men (p = 8.5 × 10?5), showing that a high naevus count on this site persists from childhood throughout life. Then, using data from 3,232 twins, we observed, in women, the lowest naevus count heritability on the trunk (26%), and the highest on the lower limbs (69%). Finally, we showed that, in 2,864 women, six genomic loci previously associated with both naevus count and melanoma risk (IRF4, DOCK8, MTAP, 9q31.2, KITLG and PLA2G6) have an effect on naevus count that is body site‐specific, but whose effect sizes are predominantly stronger on the lower limbs. Sex‐specific genetic influence on naevus count at different sites may explain differences in site‐specific melanoma incidence as well as prognosis between sexes. 相似文献
14.
Guarnera Daniele Carrera Erasmo Hansen Christopher J. Maiarù Marianna 《Biomechanics and modeling in mechanobiology》2021,20(5):1969-1980
Biomechanics and Modeling in Mechanobiology - This paper proposes a novel experimental investigation based on 3D printing to validate numerical models for biomechanics simulations. Soft elastomeric... 相似文献
15.
Jean‐Pierre Desforges Floris M. van Beest Gonalo M. Marques Stine H. Pedersen Larissa T. Beumer Marianna Chimienti Niels Martin Schmidt 《Ecology and evolution》2021,11(1):338-351
Animals have adapted behavioral and physiological strategies to conserve energy during periods of adverse conditions. Heterothermy is one such adaptation used by endotherms. While heterothermy—fluctuations in body temperature and metabolic rate—has been shown in large vertebrates, little is known of the costs and benefits of this strategy, both in terms of energy and in terms of fitness. Hence, our objective was to model the energetics of seasonal heterothermy in the largest Arctic ungulate, the muskox (Ovibos moschatus), using an individual‐based energy budget model of metabolic physiology. We found that the empirically based drop in body temperature (winter max ~−0.8°C) overwinter in adult females resulted in substantial fitness benefits in terms of reduced daily energy expenditure and body mass loss. Body mass and energy reserves were 8.98% and 14.46% greater in modeled heterotherms compared to normotherms by end of winter. Based on environmental simulations, we show that seasonal heterothermy can, to some extent, buffer the negative consequences of poor prewinter body condition or reduced winter food accessibility, leading to greater winter survival (+20%–30%) and spring energy reserves (+10%–30%), and thus increased probability of future reproductive success. These results indicate substantial adaptive short‐term benefits of seasonal heterothermy at the individual level, with potential implications for long‐term population dynamics in highly seasonal environments. 相似文献
16.
17.
18.
Humans’ ability to represent their body state from within through interoception has been proposed to predict different aspects of human cognition and behaviour. We focused on the possible contribution of interoceptive sensitivity to social behaviour as mediated by adaptive modulation of autonomic response. We, thus, investigated whether interoceptive sensitivity to one''s heartbeat predicts participants'' autonomic response at different social distances. We measured respiratory sinus arrhythmia (RSA) during either a Social or a Non-social task. In the Social task each participant viewed an experimenter performing a caress-like movement at different distances from their hand. In the Non-social task a metal stick was moved at the same distances from the participant''s hand. We found a positive association between interoceptive sensitivity and autonomic response only for the social setting. Moreover, only good heartbeat perceivers showed higher autonomic response 1) in the social compared to the non-social setting, 2) specifically, when the experimenter''s hand was moving at boundary of their peripersonal space (20 cm from the participant''s hand). Our findings suggest that interoceptive sensitivity might contribute to interindividual differences concerning social attitudes and interpersonal space representation via recruitment of different adaptive autonomic response strategies. 相似文献
19.
Background
African-American women have higher mortality from breast cancer than other ethnic groups. The association between poor survival and differences with tumor phenotypes is not well understood. The purpose of this study is to assess the clinical significance of (1) Stem cell-like markers CD44 and CD24; (2) PI3K/Akt pathway associated targets PTEN, activation of Akt, and FOXO1; and (3) the Insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP3) in different breast cancer subtypes, and compare the differences between African-American and Hispanic/Latina women who have similar social-economic-status.Methods
A total of N=318 African-American and Hispanic/Latina women, with clinically-annotated information within the inclusion criteria were included. Formalin fixed paraffin embedded tissues from these patients were tested for the different markers using immunohistochemistry techniques. Kaplan-Meier survival-curves and Cox-regression analyses were used to assess Relative Risk and Disease-Free-Survival (DFS).Results
The triple-negative-breast-cancer (TNBC) receptor-subtype was more prevalent among premenopausal women, and the Hormonal Receptor (HR) positive subtype was most common overall. TNBC tumors were more likely to have loss of PTEN, express high Ki67, and have increased CD44+/CD24- expression. TNBC was also associated with higher plasma-IGF-I levels. HR-/HER2+ tumors showed high pAkt, decreased FOXO1, and high CD24+ expression. The loss of PTEN impacted DFS significantly in African Americans, but not in Hispanics/Latinas after adjusted for treatment and other tumor pathological factors. The CD44+/CD24- and CD24+/CD44- phenotypes decreased DFS, but were not independent predictors for DFS. HER2-positive and TNBC type of cancers continued to exhibit significant decrease in DFS after adjusting for the selected biomarkers and treatment.Conclusions
TNBC incidence is high among African-American and Hispanic/Latino women residing in South Los Angeles. Our study also shows for the first time that TNBC was significantly associated with PTEN loss, high Ki67 and the CD44+/CD24- phenotype. The loss of PTEN impacts DFS significantly in African Americans. 相似文献20.
Kátia Regina da Silva Roberto Costa Elizabeth Sartori Crevelari Marianna Sobral Lacerda Caio Marcos de Moraes Albertini Martino Martinelli Filho José Eduardo Santana Jo?o Ricardo Nickenig Vissoci Ricardo Pietrobon Jacson V. Barros 《PloS one》2013,8(7)