全文获取类型
收费全文 | 351篇 |
免费 | 16篇 |
国内免费 | 1篇 |
出版年
2021年 | 12篇 |
2020年 | 5篇 |
2018年 | 9篇 |
2017年 | 7篇 |
2016年 | 12篇 |
2015年 | 23篇 |
2014年 | 12篇 |
2013年 | 17篇 |
2012年 | 15篇 |
2011年 | 12篇 |
2010年 | 16篇 |
2009年 | 11篇 |
2008年 | 10篇 |
2007年 | 14篇 |
2006年 | 6篇 |
2005年 | 5篇 |
2004年 | 11篇 |
2003年 | 5篇 |
2002年 | 13篇 |
2001年 | 11篇 |
2000年 | 11篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1994年 | 7篇 |
1993年 | 2篇 |
1992年 | 7篇 |
1991年 | 8篇 |
1990年 | 6篇 |
1989年 | 7篇 |
1988年 | 9篇 |
1987年 | 5篇 |
1986年 | 10篇 |
1985年 | 6篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1979年 | 7篇 |
1978年 | 2篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1970年 | 3篇 |
1966年 | 2篇 |
1965年 | 3篇 |
1963年 | 1篇 |
1962年 | 1篇 |
1960年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有368条查询结果,搜索用时 31 毫秒
91.
Bacterial degradation of airborne phenol in the phyllosphere 总被引:4,自引:0,他引:4
Despite the vast surface area of terrestrial plant leaves and the large microbial communities they support, little is known of the ability of leaf-associated microorganisms to access and degrade airborne pollutants. Here, we examined bacterial acquisition and degradation of phenol on leaves by an introduced phenol degrader and by natural phyllosphere communities. Whole-cell gfp-based Pseudomonas fluorescens bioreporter cells detected phenol on leaves that had previously been transiently exposed to gaseous phenol, indicating that leaves accumulated phenol; moreover, they accumulated it in sites that were accessible to epiphytic bacteria and to concentrations that were at least 10-fold higher than those in the air. After inoculated leaves were exposed to gaseous 14C-phenol, leaves harbouring the phenol-degrading Pseudomonas sp. strain CF600 released eight times more 14CO2 than did leaves harbouring a non-degrading mutant, demonstrating that CF600 actively mineralized phenol on leaves. We evaluated phenol degradation by natural microbial communities on green ash leaves that were collected from a field site rich in airborne organic pollutants. We found that significantly more phenol was mineralized by these leaves when the communities were present than by these leaves following surface sterilization. Thus, phenol-degrading organisms were present in these natural communities and were metabolically capable of phenol degradation. Collectively, these results provide the first direct evidence that bacteria on leaves can degrade an organic pollutant from the air, and indicate that bacteria on leaves could potentially contribute to the natural attenuation of organic air pollutants. 相似文献
92.
Xiangyu Chen Ray T. Suhandynata Rima Sandhu Beth Rockmill Neeman Mohibullah Hengyao Niu Jason Liang Hsiao-Chi Lo Danny E. Miller Huilin Zhou G. Valentin B?rner Nancy M. Hollingsworth 《PLoS biology》2015,13(12)
Interhomolog crossovers promote proper chromosome segregation during meiosis and are formed by the regulated repair of programmed double-strand breaks. This regulation requires components of the synaptonemal complex (SC), a proteinaceous structure formed between homologous chromosomes. In yeast, SC formation requires the “ZMM” genes, which encode a functionally diverse set of proteins, including the transverse filament protein, Zip1. In wild-type meiosis, Zmm proteins promote the biased resolution of recombination intermediates into crossovers that are distributed throughout the genome by interference. In contrast, noncrossovers are formed primarily through synthesis-dependent strand annealing mediated by the Sgs1 helicase. This work identifies a conserved region on the C terminus of Zip1 (called Zip1 4S), whose phosphorylation is required for the ZMM pathway of crossover formation. Zip1 4S phosphorylation is promoted both by double-strand breaks (DSBs) and the meiosis-specific kinase, MEK1/MRE4, demonstrating a role for MEK1 in the regulation of interhomolog crossover formation, as well as interhomolog bias. Failure to phosphorylate Zip1 4S results in meiotic prophase arrest, specifically in the absence of SGS1. This gain of function meiotic arrest phenotype is suppressed by spo11Δ, suggesting that it is due to unrepaired breaks triggering the meiotic recombination checkpoint. Epistasis experiments combining deletions of individual ZMM genes with sgs1-md zip1-4A indicate that Zip1 4S phosphorylation functions prior to the other ZMMs. These results suggest that phosphorylation of Zip1 at DSBs commits those breaks to repair via the ZMM pathway and provides a mechanism by which the crossover/noncrossover decision can be dynamically regulated during yeast meiosis. 相似文献
93.
A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation
Shih HP Kopp JL Sandhu M Dubois CL Seymour PA Grapin-Botton A Sander M 《Development (Cambridge, England)》2012,139(14):2488-2499
In the pancreas, Notch signaling is thought to prevent cell differentiation, thereby maintaining progenitors in an undifferentiated state. Here, we show that Notch renders progenitors competent to differentiate into ductal and endocrine cells by inducing activators of cell differentiation. Notch signaling promotes the expression of Sox9, which cell-autonomously activates the pro-endocrine gene Ngn3. However, at high Notch activity endocrine differentiation is blocked, as Notch also induces expression of the Ngn3 repressor Hes1. At the transition from high to intermediate Notch activity, only Sox9, but not Hes1, is maintained, thus de-repressing Ngn3 and initiating endocrine differentiation. In the absence of Sox9 activity, endocrine and ductal cells fail to differentiate, resulting in polycystic ducts devoid of primary cilia. Although Sox9 is required for Ngn3 induction, endocrine differentiation necessitates subsequent Sox9 downregulation and evasion from Notch activity via cell-autonomous repression of Sox9 by Ngn3. If high Notch levels are maintained, endocrine progenitors retain Sox9 and undergo ductal fate conversion. Taken together, our findings establish a novel role for Notch in initiating both ductal and endocrine development and reveal that Notch does not function in an on-off mode, but that a gradient of Notch activity produces distinct cellular states during pancreas development. 相似文献
94.
Rakesh S. Birjmohun Menno Vergeer Erik S. G. Stroes Manjinder S. Sandhu Sally L. Ricketts Michael W. Tanck Nicholas J. Wareham J. Wouter Jukema John J. P. Kastelein Kay-Tee Khaw S. Matthijs Boekholdt 《PloS one》2009,4(8)
Background
Paraoxonase-1 (PON1) is an antioxidant enzyme, that resides on high-density lipoprotein (HDL). PON1-activity, is heavily influenced by the PON1-Q192R polymorphism. PON1 is considered to protect against atherosclerosis, but it is unclear whether this relation is independent of its carrier, HDL. In order to evaluate the atheroprotective potential of PON1, we assessed the relationships among PON1-genotype, PON1-activity and risk of future coronary artery disease (CAD), in a large prospective case-control study.Methodology/Principal Findings
Cases (n = 1138) were apparently healthy men and women aged 45–79 years who developed fatal or nonfatal CAD during a mean follow-up of 6 years. Controls (n = 2237) were matched by age, sex and enrollment time. PON1-activity was similar in cases and controls (60.7±45.3 versus 62.6±45.8 U/L, p = 0.3) and correlated with HDL-cholesterol levels (r = 0.16, p<0.0001). The PON1-Q192R polymorphism had a profound impact on PON1-activity, but did not predict CAD risk (Odds Ratio [OR] per R allele 0.98[0.84–1.15], p = 0.8). Using conditional logistic regression, quartiles of PON1-activity showed a modest inverse relation with CAD risk (OR for the highest versus the lowest quartile 0.77[0.63–0.95], p = 0.01; p-trend = 0.06). PON1-activity adjusted for Q192R polymorphism correlated better with HDL-cholesterol (r = 0.26, p<0.0001) and more linearly predicted CAD risk (0.79[0.64–0.98], p = 0.03; p-trend = 0.008). However, these relationships were abolished after adjustment for HDL (particles-cholesterol-size) and apolipoproteinA-I (0.94[0.74–1.18], p-trend = 0.3).Conclusions/Significance
This study, shows that PON1-activity inversely relates to CAD risk, but not independent of HDL, due to its close association with the HDL-particle. These data strongly suggest that a low PON1-activity is not a causal factor in atherogenesis. 相似文献95.
Glantschnig H Hampton RA Lu P Zhao JZ Vitelli S Huang L Haytko P Cusick T Ireland C Jarantow SW Ernst R Wei N Nantermet P Scott KR Fisher JE Talamo F Orsatti L Reszka AA Sandhu P Kimmel D Flores O Strohl W An Z Wang F 《The Journal of biological chemistry》2010,285(51):40135-40147
Wnt/LRP5 signaling is a central regulatory component of bone formative and resorptive activities, and the pathway inhibitor DKK1 is a suppressor of bone formation and bone mass accrual in mice. In addition, augmented DKK1 levels are associated with high bone turnover in diverse low bone mass states in rodent models and disease etiologies in human. However, examination of the precise role of DKK1 in the normal skeleton and in higher species requires the development of refined DKK1-specific pharmacological tools. Here, we report the strategy resulting in isolation of a panel of fully human anti-DKK1 antibodies applicable to studies interrogating the roles of mouse, rhesus, and human DKK1. Selected anti-DKK1 antibodies bind primate and human DKK-1 with picomolar affinities yet do not appreciably bind to DKK2 or DKK4. Epitopes mapped within the DKK1 C-terminal domain necessary for interaction with LRP5/6 and consequently effectively neutralized DKK1 function in vitro. When introduced into naïve normal growing female mice, IgGs significantly improved trabecular bone volume and structure and increased both trabecular and cortical bone mineral densities in a dose-related fashion. Furthermore, fully human DKK1-IgG displayed favorable pharmacokinetic parameters in non-human primates. In summary, we demonstrate here a rate-limiting function of physiologic DKK1 levels in the regulation of bone mass in intact female mice, amendable to specific pharmacologic neutralization by newly identified DKK1-IgGs. Importantly the fully human IgGs display a profile of attributes that recommends their testing in higher species and their use in evaluating DKK1 function in relevant disease models. 相似文献
96.
A new mouse model (Mutatect) that permits detection of mutations at the hprt (hypoxanthine phosphoribosyltransferase) locus is described. It is highly sensitive to detection of mutants induced by clastogenic agents such as ionizing radiation. MN-11 cells are grown as a subcutaneous tumour in C57BL/6 mice for a period of 2 weeks, during which time they can be exposed to mutagenic treatments. Cells taken from the animal are cultured ex vivo and 6-thioguanine (6-TG)-resistant mutant clones can be readily identified and scored. This model system may have special utility for detecting multi-locus deletion events (chromosomal mutations) induced by high LET forms of radiation that might be encountered in space. 相似文献
97.
We report the construction and characterization of the first soybean yeast artificial chromosome (YAC) library using high-molecular weight DNA isolated from leaf nuclei of the cultivar Conrad 94 that carries Phytophthora resistance genes Rps1-k and Rps6. The quality of this library has been evaluated through analysis of 393 randomly selected YAC clones. The library consists of 36,864 clones, of which 19,956 carry single soybean YACs with an average size of about 285 kb. The library represents approximately five soybean genome equivalents. The probability of finding any soybean sequences from this library is about 0.99. The library was screened for 43 SSR markers representing the whole soybean genome. We were able to identify positive YAC pools for 95% of the SSR markers. Two YAC clones carrying molecular markers linked to the Rps6 gene were identified. The YAC library reported here would be a useful resource for map-based cloning of agronomically important soybean genes and also to complement the effort towards construction of the physical map for the soybean genome. 相似文献
98.
Altered p27(Kip1) phosphorylation, localization, and function in human epithelial cells resistant to transforming growth factor beta-mediated G(1) arrest 下载免费PDF全文
Ciarallo S Subramaniam V Hung W Lee JH Kotchetkov R Sandhu C Milic A Slingerland JM 《Molecular and cellular biology》2002,22(9):2993-3002
p27(Kip1) is an important effector of G(1) arrest by transforming growth factor beta (TGF-beta). Investigations in a human mammary epithelial cell (HMEC) model, including cells that are sensitive (184(S)) and resistant (184A1L5(R)) to G(1) arrest by TGF-beta, revealed aberrant p27 regulation in the resistant cells. Cyclin E1-cyclin-dependent kinase 2 (cdk2) and cyclin A-cdk2 activities were increased, and p27-associated kinase activity was detected in 184A1L5(R) cells. p27 from 184A1L5(R) cells was localized to both nucleus and cytoplasm, showed an altered profile of phosphoisoforms, and had a reduced ability to bind and inhibit cyclin E1-cdk2 in vitro when compared to p27 from the sensitive 184(S) cells. In proliferating 184A1L5(R) cells, more p27 was associated with cyclin D1-cdk4 complexes than in 184(S). While TGF-beta inhibited the formation of cyclin D1-cdk4-p27 complexes in 184(S) cells, it did not inhibit the assembly of cyclin D1-cdk4-p27 complexes in the resistant 184A1L5(R) cells. p27 phosphorylation changed during cell cycle progression, with cyclin E1-bound p27 in G(0) showing a different phosphorylation pattern from that of cyclin D1-bound p27 in mid-G(1). These data suggest a model in which TGF-beta modulates p27 phosphorylation from its cyclin D1-bound assembly phosphoform to an alternate form that binds tightly to inhibit cyclin E1-cdk2. Altered phosphorylation of p27 in the resistant 184A1L5(R) cells may favor the binding of p27 to cyclin D1-cdk4 and prevent its accumulation in cyclin E1-cdk2 in response to TGF-beta. 相似文献
99.
A/T-rich sequences act as quantitative enhancers of gene expression in transgenic tobacco and potato plants 总被引:10,自引:0,他引:10
The role of an A/T-rich positive regulatory region (P268, -444 to -177 from the translation start site) of the pea plastocyanin gene (PetE) promoter has been investigated in transgenic plants containing chimeric promoters fused to the -glucuronidase (GUS) reporter gene. This region enhanced GUS expression in leaves of transgenic tobacco plants when fused in either orientation to a minimal pea PetE promoter (-176 to +4) and in roots when fused in either orientation upstream or downstream of a minimal cauliflower mosaic virus 35S promoter (-90 to +5). The region was also able to enhance GUS expression in microtubers of transgenic potato plants when placed in either orientation upstream of a minimal class I patatin promoter (-332 to +14). Dissection of P268 revealed that cis elements responsible for enhancing GUS expression from the minimal PetE promoter were distributed throughout P268. Multiple copies of a 31 bp A/T-rich sequence from within P268 and of a 26 bp random A/T sequence were able to enhance GUS expression from the minimal PetE promoter, indicating that A/T-rich sequences are able to act as quantitative, non-tissue-specific enhancer elements in higher plants. Abbreviations: CaMV, cauliflower mosaic virus; GUS, -glucuronidase; HMG, high-mobility group; MAR, matrix-associated region; MU, methylumbelliferone; SAR, scaffold-associated region. 相似文献
100.
Over a 60-day experiment during the preparatory phase of the reproductive cycle, ovarian weights increased with rise in temperature in Heteropneustes fossilis and oocyte diameters suggested an optimum temperature of 22° C for Stage II oocyte formation. The oocytes did not reach Stage II at 10° C. Atresia of Stage III oocytes occurred following 60 days of exposure at 30°C. 相似文献