全文获取类型
收费全文 | 581篇 |
免费 | 92篇 |
出版年
2021年 | 7篇 |
2017年 | 8篇 |
2016年 | 10篇 |
2015年 | 17篇 |
2014年 | 15篇 |
2013年 | 38篇 |
2012年 | 16篇 |
2011年 | 12篇 |
2010年 | 12篇 |
2009年 | 10篇 |
2008年 | 20篇 |
2007年 | 16篇 |
2006年 | 17篇 |
2005年 | 22篇 |
2004年 | 17篇 |
2003年 | 11篇 |
2002年 | 19篇 |
2001年 | 19篇 |
2000年 | 19篇 |
1999年 | 10篇 |
1998年 | 10篇 |
1997年 | 5篇 |
1996年 | 10篇 |
1993年 | 7篇 |
1992年 | 16篇 |
1991年 | 9篇 |
1990年 | 10篇 |
1989年 | 9篇 |
1988年 | 6篇 |
1987年 | 10篇 |
1986年 | 9篇 |
1985年 | 12篇 |
1984年 | 7篇 |
1983年 | 14篇 |
1982年 | 14篇 |
1981年 | 10篇 |
1980年 | 10篇 |
1979年 | 8篇 |
1978年 | 8篇 |
1976年 | 12篇 |
1975年 | 7篇 |
1974年 | 10篇 |
1973年 | 9篇 |
1971年 | 9篇 |
1969年 | 8篇 |
1968年 | 4篇 |
1967年 | 4篇 |
1963年 | 4篇 |
1882年 | 5篇 |
1879年 | 6篇 |
排序方式: 共有673条查询结果,搜索用时 15 毫秒
581.
Mutation in Brca2 stimulates error-prone homology-directed repair of DNA double-strand breaks occurring between repeated sequences 总被引:16,自引:0,他引:16
Tutt A Bertwistle D Valentine J Gabriel A Swift S Ross G Griffin C Thacker J Ashworth A 《The EMBO journal》2001,20(17):4704-4716
Mutation of BRCA2 causes familial early onset breast and ovarian cancer. BRCA2 has been suggested to be important for the maintenance of genome integrity and to have a role in DNA repair by homology- directed double-strand break (DSB) repair. By studying the repair of a specific induced chromosomal DSB we show that loss of Brca2 leads to a substantial increase in error-prone repair by homology-directed single-strand annealing and a reduction in DSB repair by conservative gene conversion. These data demonstrate that loss of Brca2 causes misrepair of chromosomal DSBs occurring between repeated sequences by stimulating use of an error-prone homologous recombination pathway. Furthermore, loss of Brca2 causes a large increase in genome-wide error-prone repair of both spontaneous DNA damage and mitomycin C-induced DNA cross-links at the expense of error-free repair by sister chromatid recombination. This provides insight into the mechanisms that induce genome instability in tumour cells lacking BRCA2. 相似文献
582.
A G protein-coupled receptor for UDP-glucose 总被引:17,自引:0,他引:17
Chambers JK Macdonald LE Sarau HM Ames RS Freeman K Foley JJ Zhu Y McLaughlin MM Murdock P McMillan L Trill J Swift A Aiyar N Taylor P Vawter L Naheed S Szekeres P Hervieu G Scott C Watson JM Murphy AJ Duzic E Klein C Bergsma DJ Wilson S Livi GP 《The Journal of biological chemistry》2000,275(15):10767-10771
Uridine 5'-diphosphoglucose (UDP-glucose) has a well established biochemical role as a glycosyl donor in the enzymatic biosynthesis of carbohydrates. It is less well known that UDP-glucose may possess pharmacological activity, suggesting that a receptor for this molecule may exist. Here, we show that UDP-glucose, and some closely related molecules, potently activate the orphan G protein-coupled receptor KIAA0001 heterologously expressed in yeast or mammalian cells. Nucleotides known to activate P2Y receptors were inactive, indicating the distinctly novel pharmacology of this receptor. The receptor is expressed in a wide variety of human tissues, including many regions of the brain. These data suggest that some sugar-nucleotides may serve important physiological roles as extracellular signaling molecules in addition to their familiar role in intermediary metabolism. 相似文献
583.
Initial results of the airborne LIDAR measurement of photochemical quantum yield, ΦPo, and functional absorption cross-section, σPS II, of Photosystem II (PS II) are reported. NASA's AOL3 LIDAR was modified to implement short-pulse pump-and-probe (SP-P&P)
LIDAR measurement protocol. The prototype system is capable of measuring a pump-induced increase in probe-stimulated chlorophyll
fluorescence, ΔF/Fsat, along with the acquisition of `conventional' LIDAR-fluorosensor products from an operational altitude of 150 m. The use
of a PS II sub-saturating probe pulse increases the response signal but also results in excessive energy quenching (EEQ) affecting
the ΔF/Fsat magnitude. The airborne data indicated up to a 3-fold EEQ-caused decline in ΔF/Fsat, and 2-fold variability in the EEQ rate constant over a spatial scale a few hundred kilometers. Therefore, continuous monitoring
of EEQ parameters must be incorporated in the operational SP-P&P protocol to provide data correction for the EEQ effect. Simultaneous
airborne LIDAR measurements of ΦPo and σPS II with EEQ correction were shown to be feasible and optimal laser excitation parameters were determined. Strong daytime ΔF/Fsat decline under ambient light was found in the near-surface water layer over large aquatic areas. An example of SP-P&P LIDAR
measurement of phytoplankton photochemical and fluorescent characteristics in the Chesapeake Bay mouth is presented. Prospects
for future SP-P&P development and related problems are discussed.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
584.
Tassi E Al-Attar A Aigner A Swift MR McDonnell K Karavanov A Wellstein A 《The Journal of biological chemistry》2001,276(43):40247-40253
Fibroblast growth factor-binding protein (FGF-BP) 1 is a secreted protein that can bind fibroblast growth factors (FGFs) 1 and 2. These FGFs are typically stored on heparan sulfate proteoglycans in the extracellular matrix in an inactive form, and it has been proposed that FGF-BP1 functions as a chaperone molecule that can mobilize locally stored FGF and present the growth factor to its tyrosine kinase receptor. FGF-BP1 is up-regulated in squamous cell, colon, and breast cancers and can act as an angiogenic switch during malignant progression of epithelial cells. For the present studies, we focused on FGF-1 and -2 and investigated interactions with recombinant human FGF-BP1 protein as well as effects on signal transduction, cell proliferation, and angiogenesis. We show that recombinant FGF-BP1 specifically binds FGF-2 and that this binding is inhibited by FGF-1, heparan sulfate, and heparinoids. Furthermore, FGF-BP1 enhances FGF-1- and FGF-2-dependent proliferation of NIH-3T3 fibroblasts and FGF-2-induced extracellular signal-regulated kinase 2 phosphorylation. Finally, in the chicken chorioallantoic membrane angiogenesis assay, FGF-BP1 synergizes with exogenously added FGF-2. We conclude that FGF-BP1 binds directly to FGF-1 and FGF-2 and positively modulates the biological activities of these growth factors. 相似文献
585.
Phylogenetic relationships of the tribe Operophterini (Lepidoptera, Geometridae): a case study of the evolution of female flightlessness 总被引:1,自引:0,他引:1
NIINA SNÄLL TOOMAS TAMMARU NIKLAS WAHLBERG JAAN VIIDALEPP KAI RUOHOMÄKI MARJA-LIISA SAVONTAUS KIRSI HUOPONEN 《Biological journal of the Linnean Society. Linnean Society of London》2007,92(2):241-252
A molecular phylogenetic analysis was conducted in order to reconstruct the evolution of female flightlessness in the geometrid tribe Operophterini (Lepidoptera, Geometridae, Larentiinae). DNA variation in four nuclear gene regions, segments D1 and D2 of 28S rRNA, elongation factor 1α , and wingless , was examined from 22 species representing seven tribes of Larentiinae and six outgroup species. Direct optimization was used to infer a phylogenetic hypothesis from the combined sequence data set. The results obtained confirmed that Operophterini (including Malacodea ) is a monophyletic group, and Perizomini is its sister group. Within Operophterini, the genus Malacodea is the sister group to the genera Operophtera and Epirrita , which form a monophyletic group. This relationship is also supported by morphological data. The results suggest that female flightlessness has evolved independently twice: first in the lineage of Malacodea and, for the second time, in the lineage of Operophtera after its separation from the lineage of Epirrita . An alternative reconstruction (i.e. recovery of flight ability in an ancestor of Epirrita ) appears unlikely for various reasons. The similarities shared by Epirrita with a basal representative of Perizomini, Perizoma didymatum , allow the proposal of a sequence of evolutionary events that has led to flightlessness. It is likely that the transition to female flightlessness in the two lineages of Operophterini occurred after the colonization of stable forest habitats, followed by the evolution of a specific set of permissive traits, including larval polyphagy, limited importance of adult feeding, and adult flight during the cold months of the season. © 2007 The Linnean Society of London, Biological Journal of the Linnean Society , 2007, 92 , 241–252. 相似文献
586.
Stephanie Majkut Timon Idema Joe Swift Christine Krieger Andrea Liu Dennis E. Discher 《Current biology : CB》2013,23(23):2434-2439
- Download : Download high-res image (160KB)
- Download : Download full-size image
587.
588.
589.
590.
Zhang L Swift J Butts CA Yerubandi V Dmochowski IJ 《Journal of inorganic biochemistry》2007,101(11-12):1719-1729
A simple method for synthesizing gold nanoparticles stabilized by horse spleen apoferritin (HSAF) is reported using NaBH(4) or 3-(N-morpholino)propanesulfonic acid (MOPS) as the reducing agent. AuCl(4)(-) reduction by NaBH(4) was complete within a few seconds, whereas reduction by MOPS was much slower; in all cases, protein was required during reduction to keep the gold particles in aqueous solution. Transmission electron microscopy (TEM) showed that the gold nanoparticles were associated with the outer surface of the protein. The average particle diameters were 3.6 and 15.4 nm for NaBH(4)-reduced and MOPS-reduced Au-HSAF, respectively. A 5-nm difference in the UV-Vis absorption maximum was observed for NaBH(4)-reduced (530 nm) and MOPS-reduced Au-HSAF (535 nm), which was attributed to the greater size and aggregation of the MOPS-reduced gold sample. NaBH(4)-reduced Au-HSAF was much more effective than MOPS-reduced Au-HSAF in catalyzing the reduction of 4-nitrophenol by NaBH(4), based on the greater accessibility of the NaBH(4)-reduced gold particle to the substrate. Rapid reduction of AuCl(4)(-) by NaBH(4) was determined to result in less surface passivation by the protein. Methods for studying ferritin-gold nanoparticle assemblies may be readily applied to other protein-metal colloid systems. 相似文献