全文获取类型
收费全文 | 1108篇 |
免费 | 75篇 |
出版年
2024年 | 1篇 |
2023年 | 8篇 |
2022年 | 17篇 |
2021年 | 64篇 |
2020年 | 33篇 |
2019年 | 27篇 |
2018年 | 32篇 |
2017年 | 36篇 |
2016年 | 48篇 |
2015年 | 80篇 |
2014年 | 79篇 |
2013年 | 83篇 |
2012年 | 95篇 |
2011年 | 101篇 |
2010年 | 54篇 |
2009年 | 47篇 |
2008年 | 47篇 |
2007年 | 61篇 |
2006年 | 39篇 |
2005年 | 39篇 |
2004年 | 41篇 |
2003年 | 38篇 |
2002年 | 28篇 |
2001年 | 11篇 |
2000年 | 8篇 |
1999年 | 9篇 |
1998年 | 12篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1975年 | 1篇 |
1973年 | 2篇 |
排序方式: 共有1183条查询结果,搜索用时 281 毫秒
101.
Mesenchymal stromal cells (MSC) can be isolated from adult tissues and induced to differentiate into skeletal cells, such as osteoblasts, chondrocytes and adipocytes. Consequently, ex vivo MSC are valuable systems for studying the mechanisms that control tissue-context lineage commitment and may offer broad therapeutic applications in the orthopedic theater and beyond. To date, most of these studies have used MSC grown on two-dimensional (2-D) plastic surfaces. The use of three-dimensional (3-D) in vitro growth techniques for MSC may accelerate these areas of research by providing a more representative 'in vivo-like' environment, where cells interact with each other and their cellular products, rather than a plastic surface. We introduce some of the techniques used for 3-D in vitro cultures and how they relate to the MSC field. We will present evidence of how MSC grown as 3-D spheroids not only permits appropriate MSC-like behavior, but appears to promote their stem-cell attributes and therapeutic benefit in applications ranging from regenerative medicine to anti-inflammatory treatments and cancer therapy. 3-D culture techniques also allow de/reconstruction of the specialized in vivo niche of the tissue-resident stem cell where microenvironmental influences can be recognized. 相似文献
102.
Conrad C Wünsche A Tan TH Bulkescher J Sieckmann F Verissimo F Edelstein A Walter T Liebel U Pepperkok R Ellenberg J 《Nature methods》2011,8(3):246-249
Quantitative microscopy relies on imaging of large cell numbers but is often hampered by time-consuming manual selection of specific cells. The 'Micropilot' software automatically detects cells of interest and launches complex imaging experiments including three-dimensional multicolor time-lapse or fluorescence recovery after photobleaching in live cells. In three independent experimental setups this allowed us to statistically analyze biological processes in detail and is thus a powerful tool for systems biology. 相似文献
103.
Le Grand JN Chakrama FZ Seguin-Py S Fraichard A Delage-Mourroux R Jouvenot M Risold PY Boyer-Guittaut M 《Autophagy》2011,7(11):1302-1307
Atg8 is a yeast protein involved in the autophagic process and in particular in the elongation of autophagosomes. In mammals, several orthologs have been identified and are classed into two subfamilies: the LC3 subfamily and the GABARAP subfamily, referred to simply as the LC3 or GABARAP families. GABARAPL1 (GABARAP-like protein 1), one of the proteins belonging to the GABARAP (GABA(A) receptor-associated protein) family, is highly expressed in the central nervous system and implicated in processes such as receptor and vesicle transport as well as autophagy. The proteins that make up the GABARAP family demonstrate conservation of their amino acid sequences and protein structures. In humans, GABARAPL1 shares 86% identity with GABARAP and 61% with GABARAPL2 (GATE-16). The identification of the individual proteins is thus very limited when working in vivo due to a lack of unique peptide sequences from which specific antibodies can be developed. Actually, and to our knowledge, there are no available antibodies on the market that are entirely specific to GABARAPL1 and the same may be true of the anti-GABARAP antibodies. In this study, we sought to examine the specificity of three antibodies targeted against different peptide sequences within GABARAPL1: CHEM-CENT (an antibody raised against a short peptide sequence within the center of the protein), PTG-NTER (an antibody raised against the N-terminus of the protein) and PTG-FL (an antibody raised against the full-length protein). The results described in this article demonstrate the importance of testing antibody specificity under the conditions for which it will be used experimentally, a caution that should be taken when studying the expression of the GABARAP family proteins. 相似文献
104.
105.
PCOS (polycystic ovary syndrome) is a heterogeneous disease characterized by hyperandrogenaemia, hirsutism, oligo- or amenorrhea, insulin resistance and anovulation. The aim of the present study was to evaluate if the balance between the ovarian expression of Bax (proapoptotic protein) and Bcl-2 (antiapoptotic protein) is altered in a PCOS model developed in rats by DHEA (dehydroepiandrosterone) administration. In addition, the ovarian morphology and the circulating progesterone levels were evaluated. Histological studies confirmed the presence of follicular cysts, atretic follicles and the absence of corpora lutea in the ovaries from the PCOS group and a significant decrease in circulating progesterone levels. Immunohistochemical studies showed that the expression of Bcl-2 and Bax were mainly localized in granulosa cells of AFs (antral follicles) in both groups. Bax expression was greater in preantral and AFs from PCOS ovarian sections than in the controls. In contrast, intense Bcl-2 immunostaining was observed in the control AFs, while Bcl-2 protein was either absent in PFs (preantral follicles) or weakly expressed in AFs from PCOS rats. These results were partially confirmed by Western studies. Data revealed that the ovarian level of Bcl-2 protein was lower in PCOS than in the control and that there were no differences in Bax ovarian levels between groups. However, Bax/Bcl-2 ratio was significantly higher in PCOS group than in the control group. In conclusion, an increase in ovarian apoptosis through an imbalance among the Bcl-2 family members may be involved in the transformation of growing follicles in cystic follicles in the ovaries from DHEA-induced PCOS rats. 相似文献
106.
The GD1a glycan is a cellular receptor for adenoviruses causing epidemic keratoconjunctivitis 总被引:2,自引:0,他引:2
Nilsson EC Storm RJ Bauer J Johansson SM Lookene A Ångström J Hedenström M Eriksson TL Frängsmyr L Rinaldi S Willison HJ Pedrosa Domellöf F Stehle T Arnberg N 《Nature medicine》2011,17(1):105-109
Adenovirus type 37 (Ad37) is a leading cause of epidemic keratoconjunctivitis (EKC), a severe and highly contagious ocular disease. Whereas most other adenoviruses infect cells by engaging CD46 or the coxsackie and adenovirus receptor (CAR), Ad37 binds previously unknown sialic acid-containing cell surface molecules. By glycan array screening, we show here that the receptor-recognizing knob domain of the Ad37 fiber protein specifically binds a branched hexasaccharide that is present in the GD1a ganglioside and that features two terminal sialic acids. Soluble GD1a glycan and GD1a-binding antibodies efficiently prevented Ad37 virions from binding and infecting corneal cells. Unexpectedly, the receptor is constituted by one or more glycoproteins containing the GD1a glycan motif rather than the ganglioside itself, as shown by binding, infection and flow cytometry experiments. Molecular modeling, nuclear magnetic resonance and X-ray crystallography reveal that the two terminal sialic acids dock into two of three previously established sialic acid-binding sites in the trimeric Ad37 knob. Surface plasmon resonance analysis shows that the knob-GD1a glycan interaction has high affinity. Our findings therefore form a basis for the design and development of sialic acid-containing antiviral drugs for topical treatment of EKC. 相似文献
107.
Mateescu B Batista L Cardon M Gruosso T de Feraudy Y Mariani O Nicolas A Meyniel JP Cottu P Sastre-Garau X Mechta-Grigoriou F 《Nature medicine》2011,17(12):1627-1635
Although there is evidence that redox regulation has an essential role in malignancies, its impact on tumor prognosis remains unclear. Here we show crosstalk between oxidative stress and the miR-200 family of microRNAs that affects tumorigenesis and chemosensitivity. miR-141 and miR-200a target p38α and modulate the oxidative stress response. Enhanced expression of these microRNAs mimics p38α deficiency and increases tumor growth in mouse models, but it also improves the response to chemotherapeutic agents. High-grade human ovarian adenocarcinomas that accumulate miR-200a have low concentrations of p38α and an associated oxidative stress signature. The miR200a-dependent stress signature correlates with improved survival of patients in response to treatment. Therefore, the role of miR-200a in stress could be a predictive marker for clinical outcome in ovarian cancer. In addition, although oxidative stress promotes tumor growth, it also sensitizes tumors to treatment, which could account for the limited success of antioxidants in clinical trials. 相似文献
108.
Protein kinase signaling networks in plant innate immunity 总被引:2,自引:0,他引:2
109.
110.
Geoffrey S. Gottlieb Robert A. Smith Ndeye Mery Dia Badiane Selly Ba Stephen E. Hawes Macoumba Toure Alison K. Starling Fatou Traore Fatima Sall Stephen L. Cherne Joshua Stern Kim G. Wong Paul Lu Moon Kim Dana N. Raugi Airin Lam James I. Mullins Nancy B. Kiviat Papa Salif Sow for the UW-Dakar HIV- Study Group 《PloS one》2011,6(7)