全文获取类型
收费全文 | 22126篇 |
免费 | 2168篇 |
国内免费 | 12篇 |
出版年
2023年 | 109篇 |
2022年 | 169篇 |
2021年 | 575篇 |
2020年 | 275篇 |
2019年 | 403篇 |
2018年 | 443篇 |
2017年 | 350篇 |
2016年 | 604篇 |
2015年 | 1019篇 |
2014年 | 1063篇 |
2013年 | 1453篇 |
2012年 | 1668篇 |
2011年 | 1642篇 |
2010年 | 1011篇 |
2009年 | 885篇 |
2008年 | 1273篇 |
2007年 | 1260篇 |
2006年 | 1142篇 |
2005年 | 1091篇 |
2004年 | 987篇 |
2003年 | 905篇 |
2002年 | 876篇 |
2001年 | 251篇 |
2000年 | 216篇 |
1999年 | 223篇 |
1998年 | 196篇 |
1997年 | 166篇 |
1996年 | 131篇 |
1995年 | 131篇 |
1994年 | 140篇 |
1993年 | 128篇 |
1992年 | 155篇 |
1991年 | 155篇 |
1990年 | 150篇 |
1989年 | 122篇 |
1988年 | 135篇 |
1987年 | 126篇 |
1986年 | 105篇 |
1985年 | 134篇 |
1984年 | 138篇 |
1983年 | 98篇 |
1982年 | 101篇 |
1981年 | 98篇 |
1980年 | 101篇 |
1979年 | 119篇 |
1978年 | 87篇 |
1977年 | 89篇 |
1976年 | 104篇 |
1975年 | 101篇 |
1973年 | 86篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
21.
During the progression of malignant peritoneal mesothelioma (MPeM), tumor nodules propagate diffusely within the abdomen and tumors are characterized by distinct phenotypic sub-types. Recent studies in solid organ cancers have shown that cancer stem cells (CSCs) play a pivotal role in the initiation and progression of tumors. However, it is not known whether tumorigenic stem cells exist and whether they promote tumor growth in MPeM. In this study, we developed and characterized a CSC model for MPeM using stably expandable tumorigenic stem cells derived from patient tumors. We found morphologically distinct populations of CSCs that divide asymmetrically or symmetrically in MPeM in vitro cell culture. The MPeM stem cells (MPeMSCs) express stem cell markers c-MYC, NES and VEGFR2 and in the presence of matrix components cells form colony spheres. MPeMSCs are multipotent, differentiate into neuronal, vascular and adipose progeny upon defined induction and the differentiating cells express lineage-specific markers such as TUBB3, an early neuronal marker; vWF, VEGFA, VEGFC and IL-8, endothelial markers; and PPARγ and FABP4, adipose markers. Xenotransplantation experiments using MPeMSCs demonstrated early tumor growth compared with parental cells. Limiting dilution experiments using MPeMSCs and endothelial lineage-induced cells derived from a single MPeMSC resulted in early tumor growth in the latter group indicating that endothelial differentiation of MPeMSCs is important for MPeM tumor initiation. Our observation that the MPeM tumors contain stem cells with tumorigenic potential has important implications for understanding the cells of origin and tumor progression in MPeM and hence targeting CSCs may be a useful strategy to inhibit malignant progression. 相似文献
22.
Se-Chan Kim Alexander Ghanem Heidi Stapel Klaus Tiemann Pascal Knuefermann Andreas Hoeft Rainer Meyer Christian Grohé Anne A Knowlton Georg Baumgarten 《BMC physiology》2007,7(1):5
Backgound
It has been reported that Toll-like receptor 4 (TLR4) deficiency reduces infarct size after myocardial ischemia/reperfusion (MI/R). However, measurement of MI/R injury was limited and did not include cardiac function. In a chronic closed-chest model we assessed whether cardiac function is preserved in TLR4-deficient mice (C3H/HeJ) following MI/R, and whether myocardial and systemic cytokine expression differed compared to wild type (WT). 相似文献23.
Eliot C. Bush Anne E. Clark Chris M. DeBoever Lillian E. Haynes Sidra Hussain Singer Ma Matthew M. McDermott Adam M. Novak John S. Wentworth 《PloS one》2012,7(11)
A significant proportion of enzymes display cooperativity in binding ligand molecules, and such effects have an important impact on metabolic regulation. This is easiest to understand in the case of positive cooperativity. Sharp responses to changes in metabolite concentrations can allow organisms to better respond to environmental changes and maintain metabolic homeostasis. However, despite the fact that negative cooperativity is almost as common as positive, it has been harder to imagine what advantages it provides. Here we use computational models to explore the utility of negative cooperativity in one particular context: that of an inhibitor binding to an enzyme. We identify several factors which may contribute, and show that acting together they can make negative cooperativity advantageous. 相似文献
24.
Rasika Sunnadeniya Alexander Bean Matthew Brown Neda Akhavan Gregory Hatlestad Antonio Gonzalez V. Vaughan Symonds Alan Lloyd 《PloS one》2016,11(2)
Yellow and red-violet betalain plant pigments are restricted to several families in the order Caryophyllales, where betacyanins play analogous biological roles to anthocyanins. The initial step in betalain biosynthesis is the hydroxylation of tyrosine to form L-DOPA. Using gene expression experiments in beets, yeast, and Arabidopsis, along with HPLC/MS analysis, the present study shows that two novel cytochrome P450 (CYP450) enzymes, CYP76AD6 and CYP76AD5, and the previously described CYP76AD1 can perform this initial step. Co-expressing these CYP450s with DOPA 4,5-dioxygenase in yeast, and overexpression of these CYP450s in yellow beets show that CYP76AD1 efficiently uses L-DOPA leading to red betacyanins while CYP76AD6 and CYP76AD5 lack this activity. Furthermore, CYP76AD1 can complement yellow beetroots to red while CYP76AD6 and CYP76AD5 cannot. Therefore CYP76AD1 uniquely performs the beet R locus function and beets appear to be genetically redundant for tyrosine hydroxylation. These new functional data and ancestral character state reconstructions indicate that tyrosine hydroxylation alone was the most likely ancestral function of the CYP76AD alpha and beta groups and the ability to convert L-DOPA to cyclo-DOPA evolved later in the alpha group. 相似文献
25.
26.
Four stages of a scientific discipline; four types of scientist 总被引:1,自引:0,他引:1
Alexander M. Shneider 《Trends in biochemical sciences》2009,34(5):217-223
27.
Alexander V. Kirdyanov Eugene A. Vaganov Malcolm K. Hughes 《Trees - Structure and Function》2007,21(1):37-44
We propose a technique for separating the climatic signal which is contained in two tree-ring parameters widely used in dendroclimatology.
The method is based on the removal of the relationship between tree-ring width (TRW) and maximum latewood density (MXD) observed
for narrow tree rings from high latitudes. The new technique is tested on data from three larch stands located along the northern
timberline in Eurasia. Correlations were calculated between the temperatures of pentads (five consecutive days), TRW chronologies
and MXD chronologies calculated according to the standard and proposed methods. The analysis confirms the great importance
of summer temperature for tree radial growth and tree-ring formation. TRW is positively correlated with the temperature of
four to eight pentads (depending on the region) at the beginning of the growth season, but MXD as obtained by the standard
technique is correlated with temperature over a much longer period. For maximum density series from which the relationship
between MXD and TRW has been removed (MXD′), there is a clear correlation with temperatures in the second part of the growing
season. These results are consistent with the known dynamics of tree-ring growth in high latitudes and mechanisms of tree-ring
formation. 相似文献
28.
29.
Alexander Wiedenmann Peter Dimroth Christoph von Ballmoos 《Molecular microbiology》2009,72(2):479-490
F1 F0 ATP synthases use the electrochemical potential of H+ or Na+ across biological membranes to synthesize ATP by a rotary mechanism. In bacteria, the enzymes can act in reverse as ATP-driven ion pumps creating the indispensable membrane potential. Here, we demonstrate that the F0 parts of a Na+ - and H+ -dependent enzyme display major asymmetries with respect to their mode of operation, reflected by the requirement of ∼100 times higher Na+ or H+ concentrations for the synthesis compared with the hydrolysis of ATP. A similar asymmetry is observed during ion transport through isolated F0 parts, indicating different affinities for the binding sites in the a/c interface. Together with further data, we propose a model that provides a rationale for a differential usage of membrane potential and ion gradient during ATP synthesis as observed experimentally. The functional asymmetry might also reflect an important property of the ATP synthesis mechanism in vivo . In Escherichia coli , we observed respiratory chain-driven ATP production at pH 7–8, while P -site pH values < 6.5 were required for ATP synthesis in vitro . This discrepancy is discussed with respect to the hypothesis that during respiration lateral proton diffusion could lead to significant acidification at the membrane surface. 相似文献
30.