全文获取类型
收费全文 | 797篇 |
免费 | 90篇 |
专业分类
887篇 |
出版年
2023年 | 12篇 |
2022年 | 13篇 |
2021年 | 15篇 |
2020年 | 14篇 |
2019年 | 9篇 |
2018年 | 11篇 |
2017年 | 11篇 |
2016年 | 21篇 |
2015年 | 29篇 |
2014年 | 26篇 |
2013年 | 34篇 |
2012年 | 51篇 |
2011年 | 65篇 |
2010年 | 38篇 |
2009年 | 28篇 |
2008年 | 52篇 |
2007年 | 47篇 |
2006年 | 37篇 |
2005年 | 39篇 |
2004年 | 30篇 |
2003年 | 34篇 |
2002年 | 35篇 |
2001年 | 14篇 |
2000年 | 14篇 |
1999年 | 15篇 |
1998年 | 8篇 |
1997年 | 4篇 |
1996年 | 10篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 6篇 |
1991年 | 6篇 |
1990年 | 3篇 |
1989年 | 8篇 |
1988年 | 7篇 |
1987年 | 7篇 |
1986年 | 5篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1982年 | 6篇 |
1981年 | 11篇 |
1980年 | 16篇 |
1979年 | 16篇 |
1978年 | 12篇 |
1977年 | 6篇 |
1976年 | 11篇 |
1975年 | 5篇 |
1974年 | 11篇 |
1973年 | 3篇 |
1972年 | 5篇 |
排序方式: 共有887条查询结果,搜索用时 15 毫秒
831.
Cytochrome c can be readily adsorbed onto mesoporous silicates at high loadings of up to 10 mmol g(-)(1) of silicate. The adsorbed protein retains its peroxidative activity, with no diffusional limitations being observed. The protein can be adsorbed onto the external surface of the silicate or, provided that the pore diameter is sufficiently large, into the channels. In aqueous buffer, the catalytic activity of the adsorbed protein (for the oxidation of ABTS) decreased with increasing temperature, with the decrease being less marked for cytochrome c held within the silicate channels. Similar results were obtained in 95% methanol. Analysis of kinetic data showed that significant increases in k(cat)/K(M) occurred in methanol, ethanol, and formamide, with slight decreases occurring in 1-methoxy-2-propanol. The observed increases were primarily a result of substantial increases in k(cat), while the results in 1-methoxy-2-propanol can be ascribed to increases in K(M). Resonance Raman spectroscopy indicated that the structure of the heme environment of the adsorbed protein was essentially unchanged, in aqueous buffer and in the nonaqueous solvents, methanol, 1-methoxy-2-propanol, and ethanol. In addition, Raman spectra of the lyophilized protein indicated that there were no apparent changes in the heme structure. 相似文献
832.
Vissers LE Cox TC Maga AM Short KM Wiradjaja F Janssen IM Jehee F Bertola D Liu J Yagnik G Sekiguchi K Kiyozumi D van Bokhoven H Marcelis C Cunningham ML Anderson PJ Boyadjiev SA Passos-Bueno MR Veltman JA Smyth I Buckley MF Roscioli T 《PLoS genetics》2011,7(9):e1002278
The premature fusion of the paired frontal bones results in metopic craniosynostosis (MC) and gives rise to the clinical phenotype of trigonocephaly. Deletions of chromosome 9p22.3 are well described as a cause of MC with variably penetrant midface hypoplasia. In order to identify the gene responsible for the trigonocephaly component of the 9p22.3 syndrome, a cohort of 109 patients were assessed by high-resolution arrays and MLPA for copy number variations (CNVs) involving 9p22. Five CNVs involving FREM1, all of which were de novo variants, were identified by array-based analyses. The remaining 104 patients with MC were then subjected to targeted FREM1 gene re-sequencing, which identified 3 further mutant alleles, one of which was de novo. Consistent with a pathogenic role, mouse Frem1 mRNA and protein expression was demonstrated in the metopic suture as well as in the pericranium and dura mater. Micro-computed tomography based analyses of the mouse posterior frontal (PF) suture, the human metopic suture equivalent, revealed advanced fusion in all mice homozygous for either of two different Frem1 mutant alleles, while heterozygotes exhibited variably penetrant PF suture anomalies. Gene dosage-related penetrance of midfacial hypoplasia was also evident in the Frem1 mutants. These data suggest that CNVs and mutations involving FREM1 can be identified in a significant percentage of people with MC with or without midface hypoplasia. Furthermore, we present Frem1 mutant mice as the first bona fide mouse model of human metopic craniosynostosis and a new model for midfacial hypoplasia. 相似文献
833.
Girard F Frankel G Phillips AD Cooley W Weyer U Dugdale AH Woodward MJ La Ragione RM 《FEMS microbiology letters》2008,283(2):196-202
In this study, we used mouse ileal loops to investigate the interaction of enterohemorrhagic Escherichia coli (EHEC) O157:H7 with the mouse intestinal mucosa. With a dose of 10(9) and 3 h incubation, EHEC O157 was detected in the lumen and to a lesser extent associated with the epithelium. Typical attaching and effacing (A/E) lesions were seen, albeit infrequently. While the effector protein Tir was essential for A/E lesion formation, the bacterial type III secretion system adaptor protein TccP was dispensable. These results suggest that A/E lesions on mouse intestinal mucosa can be formed independently of robust actin polymerization. 相似文献
834.
Michael B. Cooley Michele Jay-Russell Edward R. Atwill Diana Carychao Kimberly Nguyen Beatriz Qui?ones Ronak Patel Samarpita Walker Michelle Swimley Edith Pierre-Jerome Andrew G. Gordus Robert E. Mandrell 《PloS one》2013,8(6)
During a 2.5-year survey of 33 farms and ranches in a major leafy greens production region in California, 13,650 produce, soil, livestock, wildlife, and water samples were tested for Shiga toxin (stx)-producing Escherichia coli (STEC). Overall, 357 and 1,912 samples were positive for E. coli O157:H7 (2.6%) or non-O157 STEC (14.0%), respectively. Isolates differentiated by O-typing ELISA and multilocus variable number tandem repeat analysis (MLVA) resulted in 697 O157:H7 and 3,256 non-O157 STEC isolates saved for further analysis. Cattle (7.1%), feral swine (4.7%), sediment (4.4%), and water (3.3%) samples were positive for E. coli O157:H7; 7/32 birds, 2/145 coyotes, 3/88 samples from elk also were positive. Non-O157 STEC were at approximately 5-fold higher incidence compared to O157 STEC: cattle (37.9%), feral swine (21.4%), birds (2.4%), small mammals (3.5%), deer or elk (8.3%), water (14.0%), sediment (12.3%), produce (0.3%) and soil adjacent to produce (0.6%). stx1, stx2 and stx1/stx2 genes were detected in 63%, 74% and 35% of STEC isolates, respectively. Subtilase, intimin and hemolysin genes were present in 28%, 25% and 79% of non-O157 STEC, respectively; 23% were of the “Top 6″ O-types. The initial method was modified twice during the study revealing evidence of culture bias based on differences in virulence and O-antigen profiles. MLVA typing revealed a diverse collection of O157 and non-O157 STEC strains isolated from multiple locations and sources and O157 STEC strains matching outbreak strains. These results emphasize the importance of multiple approaches for isolation of non-O157 STEC, that livestock and wildlife are common sources of potentially virulent STEC, and evidence of STEC persistence and movement in a leafy greens production environment. 相似文献
835.
836.
Recent studies have shown that anguillid eel populations in habitats spanning the marine–freshwater ecotone can display extreme
plasticity in the range of catadromy expressed by individual fishes. Carbon and nitrogen stable isotope analysis was used
to differentiate between European eels (Anguilla anguilla) collected along a short (2 km) salinity gradient ranging from <1‰ to ~30‰ in Lough Ahalia, a tidal Atlantic lake system.
Significant differences were recorded in mean δ13C, δ15N and C:N values from eels collected from fresh, brackish and marine-dominated basins. A discriminant analysis using these
predictor variables correctly classified ca. 85% of eels to salinity zone, allowing eels to be classified as freshwater (FW),
brackish (BW) or marine (MW) residents. The results of the discriminant analysis also suggested that a significant proportion
of eels moved between habitats (especially between FW and BW). Comparisons of several key population parameters showed significant
variation between eels resident in different salinity zones. Mean condition and estimated age was significantly lower in MW
eels, whilst observed length at age (a correlate of growth) was significantly higher in MW eels, intermediate in BW and lowest
in FW eels. This study has demonstrated that the ecology of eels found along a short salinity gradient can be extremely plastic
and that stable isotope analysis has considerable utility in demonstrating intra-population variation in diadromous fishes. 相似文献
837.
Organogenesis requires the differentiation and integration of distinct populations of cells to form a functional organ. In the kidney, reciprocal interactions between the ureter and the nephrogenic mesenchyme are required for organ formation. Additionally, the differentiation and integration of stromal cells are also necessary for the proper development of this organ. Much remains to be understood regarding the origin of cortical stromal cells and the pathways involved in their formation and function. By generating triple mutants in the Hox10 paralogous group genes, we demonstrate that Hox10 genes play a critical role in the developing kidney. Careful examination of control kidneys show that Foxd1-expressing stromal precursor cells are first observed in a cap-like pattern anterior to the metanephric mesenchyme and these cells subsequently integrate posteriorly into the kidney periphery as development proceeds. While the initial cap-like pattern of Foxd1-expressing cortical stromal cells is unaffected in Hox10 mutants, these cells fail to become properly integrated into the kidney, and do not differentiate to form the kidney capsule. Consistent with loss of cortical stromal cell function, Hox10 mutant kidneys display reduced and aberrant ureter branching, decreased nephrogenesis. These data therefore provide critical novel insights into the cellular and genetic mechanisms governing cortical cell development during kidney organogenesis. These results, combined with previous evidence demonstrating that Hox11 genes are necessary for patterning the metanephric mesenchyme, support a model whereby distinct populations in the nephrogenic cord are regulated by unique Hox codes, and that differential Hox function along the AP axis of the nephrogenic cord is critical for the differentiation and integration of these cell types during kidney organogenesis. 相似文献
838.
Exposure to predators does not lead to the evolution of larger brains in experimental populations of threespine stickleback 下载免费PDF全文
Kieran Samuk Jan Xue Diana J. Rennision 《Evolution; international journal of organic evolution》2018,72(4):916-929
Natural selection is often invoked to explain differences in brain size among vertebrates. However, the particular agents of selection that shape brain size variation remain obscure. Recent studies suggest that predators may select for larger brains because increased cognitive and sensory abilities allow prey to better elude predators. Yet, there is little direct evidence that exposure to predators causes the evolution of larger brains in prey species. We experimentally tested this prediction by exposing families of 1000–2000 F2 hybrid benthic‐limnetic threespine stickleback to predators under naturalistic conditions, along with matched controls. After two generations of selection, we found that fish from the predator addition treatment had significantly smaller brains (specifically smaller telencephalons and optic lobes) than fish from the control treatment. After an additional generation of selection, we reared experimental fish in a common environment and found that this difference in brain size was maintained in the offspring of fish from the predator addition treatment. Our results provide direct experimental evidence that (a) predators can indeed drive the evolution of brain size–‐but not in the fashion commonly expected and (b) that the tools of experimental evolution can be used to the study the evolution of the vertebrate brain. 相似文献
839.
The Hippo pathway is an important regulator of organ growth and cell fate. In the R8 photoreceptor cells of the Drosophila melanogaster eye, the Hippo pathway controls the fate choice between one of two subtypes that express either the blue light-sensitive Rhodopsin 5 (Hippo inactive R8 subtype) or the green light-sensitive Rhodopsin 6 (Hippo active R8 subtype). The degree to which the mechanism of Hippo signal transduction and the proteins that mediate it are conserved in organ growth and R8 cell fate choice is currently unclear. Here, we identify Crumbs and the apical spectrin cytoskeleton as regulators of R8 cell fate. By contrast, other proteins that influence Hippo-dependent organ growth, such as the basolateral spectrin cytoskeleton and Ajuba, are dispensable for the R8 cell fate choice. Surprisingly, Crumbs promotes the Rhodopsin 5 cell fate, which is driven by Yorkie, rather than the Rhodopsin 6 cell fate, which is driven by Warts and the Hippo pathway, which contrasts with its impact on Hippo activity in organ growth. Furthermore, neither the apical spectrin cytoskeleton nor Crumbs appear to regulate the Hippo pathway through mechanisms that have been observed in growing organs. Together, these results show that only a subset of Hippo pathway proteins regulate the R8 binary cell fate decision and that aspects of Hippo signalling differ between growing organs and post-mitotic R8 cells. 相似文献
840.
Hydrobiologia - Artificial drainage networks, ubiquitous within lowland agricultural landscapes in Europe and North America, exhibit a range of physical and chemical conditions, and may provide... 相似文献