全文获取类型
收费全文 | 6425篇 |
免费 | 401篇 |
国内免费 | 1篇 |
专业分类
6827篇 |
出版年
2023年 | 27篇 |
2022年 | 60篇 |
2021年 | 89篇 |
2020年 | 76篇 |
2019年 | 85篇 |
2018年 | 130篇 |
2017年 | 101篇 |
2016年 | 180篇 |
2015年 | 264篇 |
2014年 | 350篇 |
2013年 | 489篇 |
2012年 | 557篇 |
2011年 | 497篇 |
2010年 | 326篇 |
2009年 | 278篇 |
2008年 | 421篇 |
2007年 | 371篇 |
2006年 | 368篇 |
2005年 | 322篇 |
2004年 | 337篇 |
2003年 | 338篇 |
2002年 | 311篇 |
2001年 | 62篇 |
2000年 | 57篇 |
1999年 | 60篇 |
1998年 | 61篇 |
1997年 | 57篇 |
1996年 | 56篇 |
1995年 | 45篇 |
1994年 | 59篇 |
1993年 | 41篇 |
1992年 | 38篇 |
1991年 | 27篇 |
1990年 | 22篇 |
1989年 | 18篇 |
1988年 | 18篇 |
1987年 | 16篇 |
1986年 | 11篇 |
1985年 | 16篇 |
1984年 | 16篇 |
1983年 | 22篇 |
1982年 | 15篇 |
1981年 | 26篇 |
1980年 | 21篇 |
1979年 | 13篇 |
1978年 | 6篇 |
1977年 | 17篇 |
1976年 | 6篇 |
1975年 | 7篇 |
1974年 | 9篇 |
排序方式: 共有6827条查询结果,搜索用时 15 毫秒
51.
Puntoni R Filiberti R Cerrano PG Neri M Andreatta R Bonassi S 《Mutation research》2003,544(2-3):385-396
The carcinogenic effect of asbestos has been reported in the literature since 40 years, and early studies describing the epidemic occurrence of malignant mesothelioma (MM) in asbestos workers, have become a paradigm of occupational cancer research. Research on MM was abandoned for many years since MM was considered as an asbestos-related disease, interesting only from a perspective of disease control and preventive policies. The introduction of new biological endpoints in the epidemiological studies has boosted research in the field, providing new tools for the study of emerging priority in cancer research and in public health. This approach, known as molecular epidemiology has a great potential in the study of MM, contributing to the understanding of susceptibility factors, to the evaluation of cancer risk in people occupationally or environmentally exposed to carcinogens, and to the enhancement of diagnosis and therapy. A comprehensive approach based on the use of banks of biological samples is presented and its advantages discussed here. The application of innovative endpoints, such as oncoproteins in biologic fluids, genetic polimorphisms, or gene function is discussed, and relevant literature reviewed. 相似文献
52.
53.
HOTAIR role in melanoma progression and its identification in the blood of patients with advanced disease 下载免费PDF全文
54.
Contact guidance mediated three-dimensional cell migration is regulated by Rho/ROCK-dependent matrix reorganization 总被引:1,自引:0,他引:1
Cells generate mechanical force to organize the extracellular matrix (ECM) and drive important developmental and reparative processes. Likewise, tumor cells invading into three-dimensional (3D) matrices remodel the ECM microenvironment. Importantly, we previously reported a distinct radial reorganization of the collagen matrix surrounding tumors that facilitates local invasion. Here we describe a mechanism by which cells utilize contractility events to reorganize the ECM to provide contact guidance that facilitates 3D migration. Using novel assays to differentially organize the collagen matrix we show that alignment of collagen perpendicular to the tumor-explant boundary promotes local invasion of both human and mouse mammary epithelial cells. In contrast, organizing the collagen matrix to mimic the ECM organization associated with noninvading regions of tumors suppresses 3D migration/invasion. Moreover, we demonstrate that matrix reorganization is contractility-dependent and that the Rho/Rho kinase pathway is necessary for collagen alignment to provide contact guidance. Yet, if matrices are prealigned, inhibiting neither Rho nor Rho kinase inhibits 3D migration, which supports our conclusion that Rho-mediated matrix alignment is an early step in the invasion process, preceding and subsequently facilitating 3D migration. 相似文献
55.
56.
57.
Interaction computing (IC) aims to map the properties of integrable low-dimensional non-linear dynamical systems to the discrete domain of finite-state automata in an attempt to reproduce in software the self-organizing and dynamically stable properties of sub-cellular biochemical systems. As the work reported in this paper is still at the early stages of theory development it focuses on the analysis of a particularly simple chemical oscillator, the Belousov–Zhabotinsky (BZ) reaction. After retracing the rationale for IC developed over the past several years from the physical, biological, mathematical, and computer science points of view, the paper presents an elementary discussion of the Krohn–Rhodes decomposition of finite-state automata, including the holonomy decomposition of a simple automaton, and of its interpretation as an abstract positional number system. The method is then applied to the analysis of the algebraic properties of discrete finite-state automata derived from a simplified Petri net model of the BZ reaction. In the simplest possible and symmetrical case the corresponding automaton is, not surprisingly, found to contain exclusively cyclic groups. In a second, asymmetrical case, the decomposition is much more complex and includes five different simple non-abelian groups whose potential relevance arises from their ability to encode functionally complete algebras. The possible computational relevance of these findings is discussed and possible conclusions are drawn. 相似文献
58.
Vincenzo Verdoliva Cinzia Senatore Maria Letizia Polci Stefania Rossi Martina Cordella Giuseppe Carlucci Paolo Marchetti Giancarlo Antonini-Cappellini Antonio Facchiano Daniela D'Arcangelo Francesco Facchiano 《PloS one》2013,8(3)
Recently developed proteomic technologies allow to profile thousands of proteins within a high-throughput approach towards biomarker discovery, although results are not as satisfactory as expected. In the present study we demonstrate that serum proteome denaturation is a key underestimated feature; in fact, a new differential denaturation protocol better discriminates serum proteins according to their electrophoretic mobility as compared to single-denaturation protocols. Sixty nine different denaturation treatments were tested and the 3 most discriminating ones were selected (TRIDENT analysis) and applied to human sera, showing a significant improvement of serum protein discrimination as confirmed by MALDI-TOF/MS and LC-MS/MS identification, depending on the type of denaturation applied. Thereafter sera from mice and patients carrying cutaneous melanoma were analyzed through TRIDENT. Nine and 8 protein bands were found differentially expressed in mice and human melanoma sera, compared to healthy controls (p<0.05); three of them were found, for the first time, significantly modulated: α2macroglobulin (down-regulated in melanoma, p<0.001), Apolipoprotein-E and Apolipoprotein-A1 (both up-regulated in melanoma, p<0.04), both in mice and humans. The modulation was confirmed by immunological methods. Other less abundant proteins (e.g. gelsolin) were found significantly modulated (p<0.05).Conclusions: i) serum proteome contains a large amount of information, still neglected, related to proteins folding; ii) a careful serum denaturation may significantly improve analytical procedures involving complex protein mixtures; iii) serum differential denaturation protocol highlights interesting proteomic differences between cancer and healthy sera. 相似文献
59.
60.
Scala S Ieranò C Ottaiano A Franco R La Mura A Liguori G Mascolo M Staibano S Ascierto PA Botti G De Rosa G Castello G 《Cancer immunology, immunotherapy : CII》2007,56(10):1589-1595
PURPOSE: Although relatively rare, uveal melanoma is the most common ocular tumor of adults. Up to half of uveal melanoma patients die of metastatic disease. CXCR4, a chemokine receptor, is a prognostic factor in cutaneous melanoma involved in angiogenesis and metastasis formation. The aim of this study was to evaluate the expression of CXCR4 in uveal melanoma. METHODS: CXCR4 was detected by immunohistochemistry in 44 samples of uveal melanoma. Staining was categorized into three semiquantitative classes based on the rate of stained (positive) tumor cells: absence of staining, <50% of cell (+) and >50% (++). Correlations between CXCR4 expression, data on patient and tumor features were studied by contingency tables and the chi2 test. Time-to-event curves were studied using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test. Ninety-five percent confidence intervals (95% CI) of hazard ratios were also reported. RESULTS: Staining for CXCR4 protein was absent in 18 tumors (40.9%), present in <50% of cells in 19 (43.2%) and in >50% of cells in 7 (15.9%) tumors. CXCR4 expression correlated to the epithelioid-mixed cell type (P=0.030). No statistically significant relation emerged between CXCR4 expression, largest tumor diameter (LTD) and extracellular matrix patterns as evaluated through histological patterns stained with periodic acid-Schiff (PAS). Events occurred in 2 out of 18 patients (11.1%) with negative tumors (2 deaths), in 3 out of 19 patients (15.8%) with <50% of positive tumor cells (2 deaths and 1 occurrence of metastases) and in 1 out of 7 patients (14.3%) with >50% of positive tumor cells (1 occurrence of metastases). The cell type (P=0.0457) but not CXCR4 showed prognostic value at univariate analysis. CONCLUSION: This study shows that CXCR4 is commonly expressed in uveal melanoma and correlates with cell type a well-established prognostic factor. 相似文献