全文获取类型
收费全文 | 289篇 |
免费 | 42篇 |
出版年
2023年 | 3篇 |
2022年 | 2篇 |
2021年 | 3篇 |
2020年 | 3篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 10篇 |
2015年 | 6篇 |
2014年 | 7篇 |
2013年 | 13篇 |
2012年 | 14篇 |
2011年 | 22篇 |
2010年 | 11篇 |
2009年 | 13篇 |
2008年 | 19篇 |
2007年 | 17篇 |
2006年 | 13篇 |
2005年 | 17篇 |
2004年 | 13篇 |
2003年 | 11篇 |
2002年 | 13篇 |
2001年 | 11篇 |
2000年 | 7篇 |
1999年 | 9篇 |
1998年 | 6篇 |
1997年 | 5篇 |
1996年 | 10篇 |
1995年 | 2篇 |
1994年 | 6篇 |
1993年 | 4篇 |
1992年 | 10篇 |
1991年 | 7篇 |
1990年 | 9篇 |
1989年 | 5篇 |
1988年 | 2篇 |
1987年 | 7篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1980年 | 2篇 |
1977年 | 1篇 |
1975年 | 3篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1964年 | 1篇 |
排序方式: 共有331条查询结果,搜索用时 15 毫秒
61.
Thomas GH; Newbern EC; Korte CC; Bales MA; Muse SV; Clark AG; Kiehart DP 《Molecular biology and evolution》1997,14(12):1285-1295
Many structural, signaling, and adhesion molecules contain tandemly
repeated amino acid motifs. The alpha-actinin/spectrin/dystrophin
superfamily of F-actin-crosslinking proteins contains an array of triple
alpha-helical motifs (spectrin repeats). We present here the complete
sequence of the novel beta-spectrin isoform beta(Heavy)- spectrin (beta H).
The sequence of beta H supports the origin of alpha- and beta-spectrins
from a common ancestor, and we present a novel model for the origin of the
spectrins from a homodimeric actin-crosslinking precursor. The pattern of
similarity between the spectrin repeat units indicates that they have
evolved by a series of nested, nonuniform duplications. Furthermore, the
spectrins and dystrophins clearly have common ancestry, yet the repeat unit
is of a different length in each family. Together, these observations
suggest a dynamic period of increase in repeat number accompanied by
homogenization within each array by concerted evolution. However, today,
there is greater similarity of homologous repeats between species than
there is across repeats within species, suggesting that concerted evolution
ceased some time before the arthropod/vertebrate split. We propose a
two-phase model for the evolution of the spectrin repeat arrays in which an
initial phase of concerted evolution is subsequently retarded as each new
protein becomes constrained to a specific length and the repeats diverge at
the DNA level. This evolutionary model has general applicability to the
origins of the many other proteins that have tandemly repeated motifs.
相似文献
62.
Negative impacts of high temperatures on growth of black spruce forests intensify with the anticipated climate warming
下载免费PDF全文
![点击此处可从《Global Change Biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Martin P. Girardin Edward H. Hogg Pierre Y. Bernier Werner A. Kurz Xiao Jing Guo Guillaume Cyr 《Global Change Biology》2016,22(2):627-643
An increasing number of studies conclude that water limitations and heat stress may hinder the capacity of black spruce (Picea mariana (Mill.) B.S.P.) trees, a dominant species of Canada's boreal forests, to grow and assimilate atmospheric carbon. However, there is currently no scientific consensus on the future of these forests over the next century in the context of widespread climate warming. The large spatial extent of black spruce forests across the Canadian boreal forest and associated variability in climate, demography, and site conditions pose challenges for projecting future climate change responses. Here we provide an evaluation of the impacts of climate warming and drying, as well as increasing [CO2], on the aboveground productivity of black spruce forests across Canada south of 60°N for the period 1971 to 2100. We use a new extensive network of tree‐ring data obtained from Canada's National Forest Inventory, spatially explicit simulations of net primary productivity (NPP) and its drivers, and multivariate statistical modeling. We found that soil water availability is a significant driver of black spruce interannual variability in productivity across broad areas of the western to eastern Canadian boreal forest. Interannual variability in productivity was also found to be driven by autotrophic respiration in the warmest regions. In most regions, the impacts of soil water availability and respiration on interannual variability in productivity occurred during the phase of carbohydrate accumulation the year preceding tree‐ring formation. Results from projections suggest an increase in the importance of soil water availability and respiration as limiting factors on NPP over the next century due to warming, but this response may vary to the extent that other factors such as carbon dioxide fertilization, and respiration acclimation to high temperature, contribute to dampening these limitations. 相似文献
63.
Carbon and nitrogen reserves of leafy spurge (Euphorbia esula) roots as related to overwintering strategy 总被引:3,自引:0,他引:3
Leafy spurge ( Euphorbia esula L.), a serious perennial weed of temperature range and pasture lands, has continued to colonize despite various control strategies. The persistence of this species can be attributed in part to the presence of an extensive root system containing abundant organic reserves. These components, established towards the end of the growing season, are remobilized to support early spring growth. Carbohydrates comprise the bulk of reserve material with late fall incrents in free sugars being associated with reductions in starch content. Nitrogenous components undergo significant seasonal fluxes, with free amino acids and soluble proteins reaching maxima during late fall. Asparagine, glutamic acid, serine, ornithine, proline, arginine and aspartic acid all contribute significantly to the storage of nitrogen. Changes in nitrate content are associated with the overwintering process. These observations are indicative of the role that nitrogen plays in the overwintering strategy and regenerative capacity of leafy spurge roots. 相似文献
64.
65.
de Vaux St. Cyr, C. Columbia University, New York, N.Y.),and C. Howe. Immunochemical study of parainfluenza virus (type 2) in amnion cells. J. Bacteriol. 91:1911-1916. 1966.-Immunoelectrophoretic analysis of stable amnion cells in which parainfluenza virus (type 2) was being actively synthesized revealed at least three precipitating antigens not found in normal cells. These "new" antigens differed from viral neuraminidase and hemagglutinin in both specificity and electrophoretic mobility; their identity and function remain to be elucidated. 相似文献
66.
67.
Summary
Arabidopsis thaliana plants were transformed withGFPMBD (J. Marc etal., Plant Cell 10: 1927–1939, 1998) under the control of a constitutive (35S) or copper-inducible promoter. GFP
specific fluorescence distributions, levels, and persistence were determined and found to vary with age, tissue type, transgenic
line, and individual plant. With the exception of an increased frequency of abnormal roots of 35SGFP-MBD plants grown on kanamycincontaining media, expression of GFP-MBD does not appear to affect plant phenotype. The number of
leaves, branches, bolts, and siliques as well as overall height, leaf size, and seed set are similar between wild-type and
transgenic plants as is the rate of root growth. Thus, we conclude that the transgenic plants can serve as a living model
system in which the dynamic behavior of microtubules can be visualized. Confocal microscopy was used to simultaneously monitor
growth and microtubule behavior within individual cells as they passed through the elongation zone of the Arabidopsis root.
Generally, microtubules reoriented from transverse to oblique or longitudinal orientations as growth declined. Microtubule
reorientation initiated at the ends of the cell did not necessarily occur simultaneously in adjacent neighboring cells and
did not involve complete disintegration and repolymerization of microtubule arrays. Although growth rates correlated with
microtubule reorientation, the wo processes were not tightly coupled in terms of their temporal relationships, suggesting
that other factor(s) may be involved in regulating both events. Additionally, microtubule orientation was more efined in cells
whose growth was accelerating and less stringent in cells whose growth was decelerating, indicating that microtubuleorienting
factor(s) may be sensitive to growth acceleration, rather than growth per se. 相似文献
68.
Sarah M. Bronner Karl A. Merrick Jeremy Murray Laurent Salphati John G. Moffat Jodie Pang Christopher J. Sneeringer Nicholas Dompe Patrick Cyr Hans Purkey Gladys de Leon Boenig Jun Li Aleksandr Kolesnikov Robin Larouche-Gauthier Kwong Wah Lai Xiaoli Shen Samuel Aubert-Nicol Yi-Chen Chen Timothy P. Heffron 《Bioorganic & medicinal chemistry letters》2019,29(16):2294-2301
CDK4 and CDK6 are kinases with similar sequences that regulate cell cycle progression and are validated targets in the treatment of cancer. Glioblastoma is characterized by a high frequency of CDKN2A/CCND2/CDK4/CDK6 pathway dysregulation, making dual inhibition of CDK4 and CDK6 an attractive therapeutic approach for this disease. Abemaciclib, ribociclib, and palbociclib are approved CDK4/6 inhibitors for the treatment of HR+/HER2? breast cancer, but these drugs are not expected to show strong activity in brain tumors due to poor blood brain barrier penetration. Herein, we report the identification of a brain-penetrant CDK4/6 inhibitor derived from a literature molecule with low molecular weight and topological polar surface area (MW = 285 and TPSA = 66 Å2), but lacking the CDK2/1 selectivity profile due to the absence of a basic amine. Removal of a hydrogen bond donor via cyclization of the pyrazole allowed for the introduction of basic and semi-basic amines, while maintaining in many cases efflux ratios reasonable for a CNS program. Ultimately, a basic spiroazetidine (cpKa = 8.8) was identified that afforded acceptable selectivity over anti-target CDK1 while maintaining brain-penetration in vivo (mouse Kp,uu = 0.20–0.59). To probe the potency and selectivity, our lead compound was evaluated in a panel of glioblastoma cell lines. Potency comparable to abemaciclib was observed in Rb-wild type lines U87MG, DBTRG-05MG, A172, and T98G, while Rb-deficient cell lines SF539 and M059J exhibited a lack of sensitivity. 相似文献
69.
Robidoux J Kumar N Daniel KW Moukdar F Cyr M Medvedev AV Collins S 《The Journal of biological chemistry》2006,281(49):37794-37802
Catecholamine-stimulated lipolysis is primarily a beta-adrenergic and cAMP-dependent event. In previous studies we established that the beta(3)-adrenergic receptor (beta(3)AR) in adipocytes utilizes a unique mechanism to stimulate extracellular signal-regulated kinases 1 and 2 (ERK) by direct recruitment and activation of Src kinase. Therefore, we investigated the role of the ERK pathway in adipocyte metabolism and found that the beta(3)AR agonist CL316,243 regulates lipolysis through both cAMP-dependent protein kinase (PKA) and ERK. Inhibition of PKA activity completely eliminated lipolysis at low (subnanomolar) CL316,243 concentrations and by 75-80% at higher nanomolar concentrations. The remaining 20-25% of PKA-independent lipolysis, as well as ERK activation, was abolished by inhibiting the activity of either Src (PP2 or small interfering RNA), epidermal growth factor receptor (EGFR with AG1478 or small interfering RNA), or mitogen-activated protein kinase kinase 1 or 2 (MKK1/2 with PD098059). PD098059 inhibited lipolysis by 53% in mice as well. Finally, the effect of estradiol, a reported acute activator of ERK and lipolysis, was also totally prevented by PP2, AG1478, and PD098059. These results suggest that ERK activation by beta(3)AR depends upon Src and epidermal growth factor receptor kinase activities and is responsible for the PKA-independent portion of the lipolytic response. Together these results illustrate the distinct and complementary roles for PKA and ERK in catecholamine-stimulated lipolysis. 相似文献
70.
Dopaminergic dysregulation can cause motor dysfunction, but the mechanisms underlying dopamine-related motor disorders remain under debate. We used an inducible and reversible pharmacogenetic approach in dopamine transporter knockout mice to investigate the simultaneous activity of neuronal ensembles in the dorsolateral striatum and primary motor cortex during hyperdopaminergia ( approximately 500% of controls) with hyperkinesia, and after rapid and profound dopamine depletion (<0.2%) with akinesia in the same animal. Surprisingly, although most cortical and striatal neurons ( approximately 70%) changed firing rate during the transition between dopamine-related hyperkinesia and akinesia, the overall cortical firing rate remained unchanged. Conversely, neuronal oscillations and ensemble activity coordination within and between cortex and striatum did change rapidly between these periods. During hyperkinesia, corticostriatal activity became largely asynchronous, while during dopamine-depletion the synchronicity increased. Thus, dopamine-related disorders like Parkinson's disease may not stem from changes in the overall levels of cortical activity, but from dysfunctional activity coordination in corticostriatal circuits. 相似文献