全文获取类型
收费全文 | 537篇 |
免费 | 40篇 |
专业分类
577篇 |
出版年
2022年 | 5篇 |
2021年 | 7篇 |
2020年 | 9篇 |
2019年 | 9篇 |
2018年 | 4篇 |
2017年 | 6篇 |
2016年 | 16篇 |
2015年 | 24篇 |
2014年 | 30篇 |
2013年 | 26篇 |
2012年 | 34篇 |
2011年 | 37篇 |
2010年 | 18篇 |
2009年 | 11篇 |
2008年 | 24篇 |
2007年 | 35篇 |
2006年 | 31篇 |
2005年 | 35篇 |
2004年 | 34篇 |
2003年 | 35篇 |
2002年 | 30篇 |
2001年 | 4篇 |
2000年 | 5篇 |
1999年 | 6篇 |
1998年 | 6篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 9篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 4篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1976年 | 3篇 |
1974年 | 6篇 |
1971年 | 2篇 |
1970年 | 3篇 |
1969年 | 2篇 |
1964年 | 2篇 |
1963年 | 2篇 |
1962年 | 3篇 |
排序方式: 共有577条查询结果,搜索用时 0 毫秒
101.
Leila Feiz Rosalind Williams‐Carrier Susan Belcher Monica Montano Alice Barkan David B. Stern 《The Plant journal : for cell and molecular biology》2014,80(5):862-869
Ribulose‐1,5‐bisphosphate carboxylase/oxygenase (Rubisco) plays a critical role in sustaining life by catalysis of carbon fixation in the Calvin–Benson pathway. Incomplete knowledge of the assembly pathway of chloroplast Rubisco has hampered efforts to fully delineate the enzyme's properties, or seek improved catalytic characteristics via directed evolution. Here we report that a Mu transposon insertion in the Zea mays (maize) gene encoding a chloroplast dimerization co‐factor of hepatocyte nuclear factor 1 (DCoH)/pterin‐4α‐carbinolamine dehydratases (PCD)‐like protein is the causative mutation in a seedling‐lethal, Rubisco‐deficient mutant named Rubisco accumulation factor 2 (raf2‐1). In raf2 mutants newly synthesized Rubisco large subunit accumulates in a high‐molecular weight complex, the formation of which requires a specific chaperonin 60‐kDa isoform. Analogous observations had been made previously with maize mutants lacking the Rubisco biogenesis proteins RAF1 and BSD2. Chemical cross‐linking of maize leaves followed by immunoprecipitation with antibodies to RAF2, RAF1 or BSD2 demonstrated co‐immunoprecipitation of each with Rubisco small subunit, and to a lesser extent, co‐immunoprecipitation with Rubisco large subunit. We propose that RAF2, RAF1 and BSD2 form transient complexes with the Rubisco small subunit, which in turn assembles with the large subunit as it is released from chaperonins. 相似文献
102.
103.
Benjamin D Korman Chiang-Ching Huang Carly Skamra Peggy Wu Renee Koessler David Yao Qi Quan Huang William Pearce Kim Sutton-Tyrrell George Kondos Daniel Edmundowicz Richard Pope Rosalind Ramsey-Goldman 《Arthritis research & therapy》2014,16(4):R147
Introduction
Our objectives were to examine mononuclear cell gene expression profiles in patients with systemic lupus erythematosus (SLE) and healthy controls and to compare subsets with and without atherosclerosis to determine which genes’ expression is related to atherosclerosis in SLE.Methods
Monocytes were obtained from 20 patients with SLE and 16 healthy controls and were in vitro-differentiated into macrophages. Subjects also underwent laboratory and imaging studies to evaluate for subclinical atherosclerosis. Whole-genome RNA expression microarray was performed, and gene expression was examined.Results
Gene expression profiling was used to identify gene signatures that differentiated patients from controls and individuals with and without atherosclerosis. In monocytes, 9 out of 20 patients with SLE had an interferon-inducible signature compared with 2 out of 16 controls. By looking at gene expression during monocyte-to-macrophage differentiation, we identified pathways which were differentially regulated between SLE and controls and identified signatures based on relevant intracellular signaling molecules which could differentiate SLE patients with atherosclerosis from controls. Among patients with SLE, we used a previously defined 344-gene atherosclerosis signature in monocyte-to-macrophage differentiation to identify patient subgroups with and without atherosclerosis. Interestingly, this signature further classified patients on the basis of the presence of SLE disease activity and cardiovascular risk factors.Conclusions
Many genes were differentially regulated during monocyte-to-macrophage differentiation in SLE patients compared with controls. The expression of these genes in mononuclear cells is important in the pathogenesis of SLE, and molecular profiling using gene expression can help stratify SLE patients who may be at risk for development of atherosclerosis. 相似文献104.
Simon J. Tunster Mathew Van De Pette Rosalind M. John 《Disease models & mechanisms》2014,7(10):1185-1191
Pleckstrin homology-like domain family A member 2 (PHLDA2) is a maternally expressed imprinted gene whose elevated expression has been linked to fetal growth restriction in a number of human studies. In mice, Phlda2 negatively regulates placental growth and limits the accumulation of placental glycogen. We previously reported that a three-copy transgene spanning the Phlda2 locus drove a fetal growth restriction phenotype late in gestation, suggesting a causative role for PHLDA2 in human growth restriction. However, in this mouse model, Phlda2 was overexpressed by fourfold, alongside overexpression of a second imprinted gene, Slc22a18. Here, we genetically isolate the role of Phlda2 in driving late fetal growth restriction in mice. We furthermore show that this Phlda2-driven growth restriction is asymmetrical, with a relative sparing of the brain, followed by rapid catch-up growth after birth, classic features of placental insufficiency. Strikingly, fetal growth restriction showed strain-specific differences, being apparent on the 129S2/SvHsd (129) genetic background and absent on the C57BL6 (BL6) background. A key difference between these two strains is the placenta. Specifically, BL6 placentae possess a more extensive endocrine compartment and substantially greater stores of placental glycogen. Taken together, these data support a direct role for elevated Phlda2 in limiting fetal growth but also suggest that growth restriction only manifests when there is limited placental reserve. These findings should be taken into account in interpreting the results from human studies.KEY WORDS: Phlda2, Fetal growth restriction, Asymmetric 相似文献
105.
Karen D. Bradham Brian D. Laird Pat E. Rasmussen Rosalind A. Schoof Sophia M. Serda Steven D. Siciliano 《人类与生态风险评估》2014,20(1):272-286
Exposure to contaminated soil and dust is an important pathway in human health risk assessment. Physical and chemical characteristics and biological factors determine the bioaccessibility/bioavailability of soil and dust contaminants. Within a single sample, contamination may arise from multiple sources of toxic elements that may exist as different species that impact bioavailability. In turn, the bioaccessibility/bioavailability of soil and dust contaminants directly impacts human health risk. Research efforts focusing on development and application of in vitro and in vivo methods to measure the bioaccessibility/bioavailability of metal-contaminated soils have advanced in recent years. The objective of this workshop was to focus on developments in assessing the bioaccessibility/bioavailability of arsenic-contaminated soils, metals’ contamination in urban Canadian residences and potential children's exposures to toxic elements in house dust, an urban community-based study (i.e., West Oakland Residential Lead Assessment), bioavailability studies of soil cadmium, chromium, nickel, and mercury and human exposures to contaminated Brownfield soils. These presentations covered issues related to human health and bioavailability along with the most recent studies on community participation in assessing metals’ contamination, studies of exposures to residential contamination, and in vitro and in vivo methods development for assessing the bioaccessibility/bioavailability of metals in soils and dusts. 相似文献
106.
Bradley A. Heller Monica Ghidinelli Jakob Voelkl Steven Einheber Ryan Smith Ethan Grund Grant Morahan David Chandler Luba Kalaydjieva Filippo Giancotti Rosalind H. King Aniko Naray Fejes-Toth Gerard Fejes-Toth Maria Laura Feltri Florian Lang James L. Salzer 《The Journal of cell biology》2014,204(7):1219-1236
The PI 3-kinase (PI 3-K) signaling pathway is essential for Schwann cell myelination. Here we have characterized PI 3-K effectors activated during myelination by probing myelinating cultures and developing nerves with an antibody that recognizes phosphorylated substrates for this pathway. We identified a discrete number of phospho-proteins including the S6 ribosomal protein (S6rp), which is down-regulated at the onset of myelination, and N-myc downstream-regulated gene-1 (NDRG1), which is up-regulated strikingly with myelination. We show that type III Neuregulin1 on the axon is the primary activator of S6rp, an effector of mTORC1. In contrast, laminin-2 in the extracellular matrix (ECM), signaling through the α6β4 integrin and Sgk1 (serum and glucocorticoid-induced kinase 1), drives phosphorylation of NDRG1 in the Cajal bands of the abaxonal compartment. Unexpectedly, mice deficient in α6β4 integrin signaling or Sgk1 exhibit hypermyelination during development. These results identify functionally and spatially distinct PI 3-K pathways: an early, pro-myelinating pathway driven by axonal Neuregulin1 and a later-acting, laminin–integrin-dependent pathway that negatively regulates myelination. 相似文献
107.
108.
Masochistic dreams, as defined by Beck (1967), are reportedly more prevalent among women and individuals with past or present depression. However, it is unclear whether these prevalence differences are a function of depressogenic personality traits or fluctuating mood symptoms. In the present study, 30 men and 30 women without histories of major depression slept two consecutive nights in a sleep laboratory and reported their dreams from each REM period on the second night. Dream content from this sample was compared to that of 60 depressed participants who were studied previously under the same protocol. Analyses did not support a heightened prevalence of masochistic dreams among women or depressed individuals. Interestingly, the masochistic dreams of the non-depressed sample were equally distributed across the night, whereas depressed individuals tend to report masochistic dreams closer to morning. This hypothesized pattern suggests that masochistic dreams may be pathognomic of depression in that their occurrence near the end of the night affects morning mood with negative dream residue. 相似文献
109.
110.
We report for the first time an analysis of the ATPase activity of human DNA topoisomerase (topo) IIβ. We show that topo IIβ is a DNA-dependent ATPase that appears to fit Michaelis–Menten kinetics. The ATPase activity is stimulated 44-fold by DNA. The kcat for ATP hydrolysis by human DNA topo IIβ in the presence of DNA is 2.25 s–1. We have characterised a topo IIβ derivative which carries a mutation in the ATPase domain (S165R). S165R reduced the kcat for ATP hydrolysis by 7-fold, to 0.32 s–1, while not significantly altering the apparent Km. The specificity constant for the interaction between ATP and topo IIβ (kcat/Kmapp) showed a 90% reduction for βS165R. The DNA binding affinity and ATP-independent DNA cleavage activity of the enzyme are unaffected by this mutation. However, the strand passage activity is reduced by 80%, presumably due to reduced ATP hydrolysis. The mutant enzyme is unable to complement ts yeast topo II in vivo. We have used computer modelling to predict the arrangement of key residues at the ATPase active site of topo IIβ. Ser165 is predicted to lie very close to the bound nucleotide, and the S165R mutation could thus influence both ATP binding and ADP dissociation. 相似文献