全文获取类型
收费全文 | 828篇 |
免费 | 98篇 |
专业分类
926篇 |
出版年
2023年 | 13篇 |
2021年 | 12篇 |
2020年 | 6篇 |
2019年 | 23篇 |
2018年 | 17篇 |
2017年 | 20篇 |
2016年 | 26篇 |
2015年 | 37篇 |
2014年 | 32篇 |
2013年 | 46篇 |
2012年 | 53篇 |
2011年 | 48篇 |
2010年 | 34篇 |
2009年 | 28篇 |
2008年 | 41篇 |
2007年 | 54篇 |
2006年 | 44篇 |
2005年 | 47篇 |
2004年 | 49篇 |
2003年 | 42篇 |
2002年 | 45篇 |
2001年 | 11篇 |
2000年 | 23篇 |
1999年 | 11篇 |
1998年 | 11篇 |
1997年 | 8篇 |
1996年 | 14篇 |
1995年 | 6篇 |
1994年 | 9篇 |
1993年 | 10篇 |
1992年 | 4篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 7篇 |
1987年 | 7篇 |
1986年 | 6篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1979年 | 3篇 |
1978年 | 7篇 |
1977年 | 4篇 |
1975年 | 5篇 |
1974年 | 5篇 |
1973年 | 3篇 |
1949年 | 3篇 |
1905年 | 2篇 |
排序方式: 共有926条查询结果,搜索用时 15 毫秒
31.
Martin SP Townsend RJ Kuznetsova LA Borthwick KA Hill M McDonnell MB Coakley WT 《Biosensors & bioelectronics》2005,21(5):758-767
The capture of Bacillus subtilis var. niger spores on an antibody-coated surface can be enhanced when that coated surface acts as an acoustic reflector in a quarter wavelength ultrasonic (3 MHz) standing wave resonator. Immunocapture in such a resonator has been characterised here for both spores and 1 microm diameter biotinylated fluorescent microparticles. A mean spatial acoustic pressure amplitude of 460 kPa and a frequency of 2.82 MHz gave high capture efficiencies. It was shown that capture was critically dependent on reflector thickness. The time dependence of particle deposition on a reflector in a batch system was broadly consistent with a calculated time of 35 s to bring 95% of particles to the coated surface. A suspension flow rate of 0.1 ml/min and a reflector thickness of 1.01 mm gave optimal capture in a 2 min assay. The enhancement of particle detection compared with the control (no ultrasound) situation was x 70. The system detects a total of five particles in 15 fields of view in a 2 min assay when the suspending phase concentration was 10(4) particles/ml. A general expression for the dependence of minimum concentration detectable on; number of fields examined, sample volume flowing through the chamber and assay time shows that, for a practical combination of these variables, the threshold detection concentration can be two orders of magnitude lower. 相似文献
32.
Radiation capture and conversion efficiencies of Miscanthus sacchariflorus,M. sinensis and their naturally occurring hybrid M. × giganteus 下载免费PDF全文
Christopher Lyndon Davey Laurence Edmund Jones Michael Squance Sarah Jane Purdy Anne Louise Maddison Jennifer Cunniff Iain Donnison John Clifton‐Brown 《Global Change Biology Bioenergy》2017,9(2):385-399
Miscanthus is a rhizomatous C4 grass of great interest as a biofuel crop because it has the potential to produce high yields over a wide geographical area with low agricultural inputs on marginal land less suitable for food production. At the moment, a clonal interspecific hybrid Miscanthus × giganteus is the most widely cultivated and studied in Europe and the United States, but breeding programmes are developing newer more productive varieties. Here, we quantified the physiological processes relating to whole season yield in a replicated plot trial in Wales, UK. Light capture and conversion efficiency were parameterized for four carefully selected genotypes (M. sinensis, M. sacchariflorus and Miscanthus × giganteus). Differences in the canopy architecture in mature stands as measured by the extinction coefficient (k) were small (0.55–0.65). Sensitivity analysis on a mathematical model of Miscanthus was performed to quantify the accumulative intercepted photosynthetically active radiation (iPAR) in the growing season using (i) k, (ii) variation in the thermal responses of leaf expansion rate, (iii) base temperature for degree days and (iv) date start of canopy expansion. A 10% increase in k or leaf area per degree day both had a minimal effect on iPAR (3%). Decreasing base temperature from 10 to 9 °C gave an 8% increase in iPAR. If the starting date for canopy expansion was the same as shoot emergence date, then the iPAR increases by 12.5%. In M. × giganteus, the whole season above ground and total (including below ground) radiation‐use efficiency (RUE) ranged from 45% to 37% higher than the noninterspecific hybrid genotypes. The greater yields in the interspecific hybrid M. × giganteus are explained by the higher RUE and not by differences in iPAR or partitioning effects. Studying the mechanisms underlying this complex trait could have wide benefits for both fuel and food production. 相似文献
33.
Oana Coban Laura?C. Zanetti-Dominguez Daniel?R. Matthews Daniel?J. Rolfe Gregory Weitsman Paul?R. Barber Jody Barbeau Viviane Devauges Florian Kampmeier Martyn Winn Borivoj Vojnovic Peter?J. Parker Keith?A. Lidke Diane?S. Lidke Simon?M. Ameer-Beg Marisa?L. Martin-Fernandez Tony Ng 《Biophysical journal》2015,108(5):1013-1026
Deregulation of epidermal growth factor receptor (EGFR) signaling has been correlated with the development of a variety of human carcinomas. EGF-induced receptor dimerization and consequent trans- auto-phosphorylation are among the earliest events in signal transduction. Binding of EGF is thought to induce a conformational change that consequently unfolds an ectodomain loop required for dimerization indirectly. It may also induce important allosteric changes in the cytoplasmic domain. Despite extensive knowledge on the physiological activation of EGFR, the effect of targeted therapies on receptor conformation is not known and this particular aspect of receptor function, which can potentially be influenced by drug treatment, may in part explain the heterogeneous clinical response among cancer patients. Here, we used Förster resonance energy transfer/fluorescence lifetime imaging microscopy (FRET/FLIM) combined with two-color single-molecule tracking to study the effect of ATP-competitive small molecule tyrosine kinase inhibitors (TKIs) and phosphatase-based manipulation of EGFR phosphorylation on live cells. The distribution of dimer on-times was fitted to a monoexponential to extract dimer off-rates (koff). Our data show that pretreatment with gefitinib (active conformation binder) stabilizes the EGFR ligand-bound homodimer. Overexpression of EGFR-specific DEP-1 phosphatase was also found to have a stabilizing effect on the homodimer. No significant difference in the koff of the dimer could be detected when an anti-EGFR antibody (425 Snap single-chain variable fragment) that allows for dimerization of ligand-bound receptors, but not phosphorylation, was used. These results suggest that both the conformation of the extracellular domain and phosphorylation status of the receptor are involved in modulating the stability of the dimer. The relative fractions of these two EGFR subpopulations (interacting versus free) were obtained by a fractional-intensity analysis of ensemble FRET/FLIM images. Our combined imaging approach showed that both the fraction and affinity (surrogate of conformation at a single-molecule level) increased after gefitinib pretreatment or DEP-1 phosphatase overexpression. Using an EGFR mutation (I706Q, V948R) that perturbs the ability of EGFR to dimerize intracellularly, we showed that a modest drug-induced increase in the fraction/stability of the EGFR homodimer may have a significant biological impact on the tumor cell’s proliferation potential. 相似文献
34.
Ailbhe M. McDermott Nicola Miller Deirdre Wall Lorcan M. Martyn Graham Ball Karl J. Sweeney Michael J. Kerin 《PloS one》2014,9(1)
Introduction
Breast cancer is a common disease with distinct tumor subtypes phenotypically characterized by ER and HER2/neu receptor status. MiRNAs play regulatory roles in tumor initiation and progression, and altered miRNA expression has been demonstrated in a variety of cancer states presenting the potential for exploitation as cancer biomarkers. Blood provides an excellent medium for biomarker discovery. This study investigated systemic miRNAs differentially expressed in Luminal A-like (ER+PR+HER2/neu-) breast cancer and their effectiveness as oncologic biomarkers in the clinical setting.Methods
Blood samples were prospectively collected from patients with Luminal A-like breast cancer (n = 54) and controls (n = 56). RNA was extracted, reverse transcribed and subjected to microarray analysis (n = 10 Luminal A-like; n = 10 Control). Differentially expressed miRNAs were identified by artificial neural network (ANN) data-mining algorithms. Expression of specific miRNAs was validated by RQ-PCR (n = 44 Luminal A; n = 46 Control) and potential relationships between circulating miRNA levels and clinicopathological features of breast cancer were investigated.Results
Microarray analysis identified 76 differentially expressed miRNAs. ANN revealed 10 miRNAs for further analysis (miR-19b, miR-29a, miR-93, miR-181a, miR-182, miR-223, miR-301a, miR-423-5p, miR-486-5 and miR-652). The biomarker potential of 4 miRNAs (miR-29a, miR-181a, miR-223 and miR-652) was confirmed by RQ-PCR, with significantly reduced expression in blood of women with Luminal A-like breast tumors compared to healthy controls (p = 0.001, 0.004, 0.009 and 0.004 respectively). Binary logistic regression confirmed that combination of 3 of these miRNAs (miR-29a, miR-181a and miR-652) could reliably differentiate between cancers and controls with an AUC of 0.80.Conclusion
This study provides insight into the underlying molecular portrait of Luminal A-like breast cancer subtype. From an initial 76 miRNAs, 4 were validated with altered expression in the blood of women with Luminal A-like breast cancer. The expression profiles of these 3 miRNAs, in combination with mammography, has potential to facilitate accurate subtype-specific breast tumor detection. 相似文献35.
Martyn Humphries Jozef Nemcek John B. Cantwell John J. Gerrard 《FEMS microbiology letters》1987,45(5):297-304
Twelve graft copolymers have been evaluated for their ability to prevent the adhesion of bacteria to substrata. The copolymers had polyethylene glycol (PEG) side-chains (‘teeth’) and a backbone that was either uncharged, acidic, basic or amphoteric. The copolymers were adsorbed onto glass, stainless steel and hydroxyapatite substrata, and 2-hpetri-dish adhesion experiments performed with bacteria isolated from marine (Pseudomonas sp. NCMB 2021), paper mill (S. marcescens NCIB 12211) and oral (S. mutans NCTC 10449) environments. The copolymers containing the most charged groups in the backbone had the most significant effect on bacterial adhesion levels, with anti-adhesive effects up to 99% achieved. An amphoteric copolymer (Compound 12) on glass, and acidic copolymer (Compound 11) on stainless steel and hydroxyapatite gave the most impressive anti-adhesive effects. These copolymers had non-specific bacterial anti-adhesive properties.It is proposed that the graft copolymers adsorbed onto hydrophilic surfaces via their charged backbone in such a way that the PEG side-chains were pointing out into the aqueous phase, and it was this orientation that was responsible for the observed anti-adhesive effect. 相似文献
36.
Maintaining connexin43 gap junctional communication in v-Src cells does not alter growth properties associated with the transformed phenotype 总被引:1,自引:0,他引:1
Loss of connexin expression and/or gap junctional communication (GJC) has been correlated with increased rates of cell growth in tumor cells compared to their normal communication-competent counterparts. Conversely, reduced rates of cell growth have been observed in tumor cells that are induced to express exogenous connexins and re-establish GJC. It is not clear how this putative growth-suppressive effect of the connexin proteins is mediated and some data has suggested that this function may be independent of GJC. In mammalian cells that express v-Src, connexin43 (Cx43) is phosphorylated on Tyr247 and Tyr265 and this results in a dramatic disruption of GJC. Cells that express a Cx43 mutant with phenylalanine mutations at these tyrosine sites form functional gap junctions that, unlike junctions formed by wild type Cx43, remain functional in cells that co-express v-Src. These cells still appear transformed; however, it is not known whether their ability to maintain GJC prevents the loss of growth restraints that confine "normal" cells, such as the inability to grow in an anchorage-independent manner or to form foci. In these studies, we have examined some of the growth properties of cells with Cx43 gap junctions that remain communication-competent in the presence of the co-expressed v-Src oncoprotein. 相似文献
37.
Anita Shepherd Danny Awty-Carroll Jason Kam Chris Ashman Elena Magenau Enrico Martani Mislav Kontek Andrea Ferrarini Stefano Amaducci Chris Davey Vanja Jurišić Gert-Jan Petrie Mohamad Al Hassan Isabelle Lamy Iris Lewandowski Emmanuel de Maupeou Jon McCalmont Luisa Trindade Kasper van der Cruijsen Philip van der Pluijm Rebecca Rowe Andrew Lovett Iain Donnison Andreas Kiesel John Clifton-Brown Astley Hastings 《Global Change Biology Bioenergy》2023,15(4):444-461
New biomass crop hybrids for bioeconomic expansion require yield projections to determine their potential for strategic land use planning in the face of global challenges. Our biomass growth simulation incorporates radiation interception and conversion efficiency. Models often use leaf area to predict interception which is demanding to determine accurately, so instead we use low-cost rapid light interception measurements using a simple laboratory-made line ceptometer and relate the dynamics of canopy closure to thermal time, and to measurements of biomass. We apply the model to project the European biomass potentials of new market-ready hybrids for 2020–2030. Field measurements are easier to collect, the calibration is seasonally dynamic and reduces influence of weather variation between field sites. The model obtained is conservative, being calibrated by crops of varying establishment and varying maturity on less productive (marginal) land. This results in conservative projections of miscanthus hybrids for 2020–2030 based on 10% land use conversion of the least (productive) grassland and arable for farm diversification, which show a European potential of 80.7–89.7 Mt year−1 biomass, with potential for 1.2–1.3 EJ year−1 energy and 36.3–40.3 Mt year−1 carbon capture, with seeded Miscanthus sacchariflorus × sinensis displaying highest yield potential. Simulated biomass projections must be viewed in light of the field measurements on less productive land with high soil water deficits. We are attempting to model the results from an ambitious and novel project combining new hybrids across Europe with agronomy which has not been perfected on less productive sites. Nevertheless, at the time of energy sourcing issues, seed-propagated miscanthus hybrids for the upscaled provision of bioenergy offer an alternative source of renewable energy. If European countries provide incentives for growers to invest, seeded hybrids can improve product availability and biomass yields over the current commercial miscanthus variety. 相似文献
38.
Silke Kuphal Adam C. Martyn Julie Pedley Lisa M. Crowther Vanessa F. Bonazzi Peter G. Parsons Anja K. Bosserhoff Nicholas K. Hayward Glen M. Boyle 《Pigment cell & melanoma research》2009,22(3):296-306
Melanocytic behavior, survival, and proliferation are regulated through a complex system of cell–cell adhesion molecules. Pathologic changes leading to development of malignant melanoma, upset the delicate homeostatic balance between melanocytes and keratinocytes and can lead to altered expression of cell–cell adhesion and cell–cell communication molecules. Malignant transformation of melanocytes frequently coincides with loss of E‐cadherin expression. We now show loss of another member of the superfamily of classical cadherins, H‐cadherin (CDH13), which may be involved in the development of malignant melanoma. The provided data show that H‐cadherin expression is lost in nearly 80% of the analyzed melanoma cell lines. Knockdown of H‐cadherin using siRNA increases invasive capacity in melanocytes. Functional assays show that the re‐expression of H‐cadherin decreases migration and invasion capacity, as well as anchorage‐independent growth in comparison to control melanoma cells. Furthermore, melanoma cells, which re‐express H‐cadherin via stable transfection show a reduction in rate of tumor growth in a nu/nu mouse tumor model in comparison to the parental control transfected cell lines. Our study presents for the first time the down‐regulation of H‐cadherin in malignant melanomas and its possible functional relevance in maintenance healthy skin architecture. 相似文献
39.
Role of JC virus agnoprotein in DNA repair 总被引:2,自引:0,他引:2
Darbinyan A Siddiqui KM Slonina D Darbinian N Amini S White MK Khalili K 《Journal of virology》2004,78(16):8593-8600
40.