全文获取类型
收费全文 | 2211篇 |
免费 | 161篇 |
国内免费 | 1篇 |
专业分类
2373篇 |
出版年
2024年 | 1篇 |
2023年 | 12篇 |
2022年 | 42篇 |
2021年 | 57篇 |
2020年 | 17篇 |
2019年 | 42篇 |
2018年 | 81篇 |
2017年 | 50篇 |
2016年 | 71篇 |
2015年 | 106篇 |
2014年 | 129篇 |
2013年 | 172篇 |
2012年 | 189篇 |
2011年 | 201篇 |
2010年 | 132篇 |
2009年 | 111篇 |
2008年 | 122篇 |
2007年 | 165篇 |
2006年 | 144篇 |
2005年 | 119篇 |
2004年 | 111篇 |
2003年 | 110篇 |
2002年 | 83篇 |
2001年 | 24篇 |
2000年 | 5篇 |
1999年 | 13篇 |
1998年 | 12篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 8篇 |
1994年 | 2篇 |
1993年 | 6篇 |
1992年 | 5篇 |
1990年 | 2篇 |
1988年 | 4篇 |
1987年 | 6篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1981年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有2373条查询结果,搜索用时 15 毫秒
71.
Bayesian Modeling of the Yeast SH3 Domain Interactome Predicts Spatiotemporal Dynamics of Endocytosis Proteins 下载免费PDF全文
Raffi Tonikian Xiaofeng Xin Christopher P. Toret David Gfeller Christiane Landgraf Simona Panni Serena Paoluzi Luisa Castagnoli Bridget Currell Somasekar Seshagiri Haiyuan Yu Barbara Winsor Marc Vidal Mark B. Gerstein Gary D. Bader Rudolf Volkmer Gianni Cesareni David G. Drubin Philip M. Kim Sachdev S. Sidhu Charles Boone 《PLoS biology》2009,7(10)
SH3 domains are peptide recognition modules that mediate the assembly of diverse biological complexes. We scanned billions of phage-displayed peptides to map the binding specificities of the SH3 domain family in the budding yeast, Saccharomyces cerevisiae. Although most of the SH3 domains fall into the canonical classes I and II, each domain utilizes distinct features of its cognate ligands to achieve binding selectivity. Furthermore, we uncovered several SH3 domains with specificity profiles that clearly deviate from the two canonical classes. In conjunction with phage display, we used yeast two-hybrid and peptide array screening to independently identify SH3 domain binding partners. The results from the three complementary techniques were integrated using a Bayesian algorithm to generate a high-confidence yeast SH3 domain interaction map. The interaction map was enriched for proteins involved in endocytosis, revealing a set of SH3-mediated interactions that underlie formation of protein complexes essential to this biological pathway. We used the SH3 domain interaction network to predict the dynamic localization of several previously uncharacterized endocytic proteins, and our analysis suggests a novel role for the SH3 domains of Lsb3p and Lsb4p as hubs that recruit and assemble several endocytic complexes. 相似文献
72.
Nitrous oxide and methane fluxes from soils of the Orinoco savanna under different land uses 总被引:2,自引:0,他引:2
Castaldi Simona De Pascale Raffaele Ariangelo Grace John† Nikonova Nina§ Montes Ruben§ San José José‡ 《Global Change Biology》2004,10(11):1947-1960
The study investigates the effect of land‐use change on nitrous oxide (N2O) and methane (CH4) fluxes from soil, in savanna ecosystems of the Orinoco region (Venezuela). Gas fluxes were measured by closed static chambers, in the wet and dry season, in representative systems of land management of the region: a cultivated pasture, an herbaceous savanna, a tree savanna and a woodland (control site). Higher N2O emissions were observed in the cultivated pasture and in the herbaceous savanna compared with the tree savanna and the woodland, and differences were mainly related to fine soil particle content and soil volumetric water content measured in the studied sites. Overall N2O emissions were quite low in all sites (0–1.58 mg N2O‐N m?2 day?1). The cultivated pasture and the woodland savanna were on average weak CH4 sinks (?0.05±0.07 and ?0.08±0.05 mg CH4 m?2 day?1, respectively), whereas the herbaceous savanna and the tree savanna showed net CH4 production (0.23±0.05 and 0.19±0.05 mg CH4 m?2 day?1, respectively). Variations of CH4 fluxes were mainly driven by variation of soil water‐filled pore space (WFPS), and a shift from net CH4 consumption to net CH4 production was observed at around 30% WFPS. Overall, the data suggest that conversion of woodland savanna to managed landscape could alter both CH4 and N2O fluxes; however, the magnitude of such variation depends on the soil characteristics and on the type of land management before conversion. 相似文献
73.
Tiziano Fossati Simona Parisi Gianalfredo Abbiati Carlo Castiglioni 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1992,577(2)
A high-performance liquid chromatographic method for the determination of picotamide in human plasma and urine is described. After addition of an internal standard (bamifylline), the plasma and urine samples were subjected to liquid—liquid extraction and clean-up procedures. The final extracts were evaporated to dryness and the resulting residues were reconstituted in 100 μl of methanol—water (50:50, v/v) and chromatographed on a LiChrosorb RP-SELECT B reversed-phase column coupled to an ultraviolet detector monitored at 230 nm. Chromatographic analysis takes about 10 min per sample. The assay was linear over a wide range and has a limit of detection of 0.005 and 0.1 μg/ml in plasma and urine, respectively. It was selective for picotamide, accurate and robust and thus suitable for routine assays after therapeutic doses of picotamide. 相似文献
74.
Othman Al Musaimi Sophie V. Morse Lucia Lombardi Simona Serban Alessandra Basso Daryl R. Williams 《Journal of peptide science》2023,29(2):e3448
Successful manual synthesis of the TD2.2 peptide acting as a blood–brain barrier shuttle was achieved. TD2.2 was successfully synthesised by sequential condensation of four protected peptide fragments on solid-phase settings, after several unsuccessful attempts using the stepwise approach. These fragments were chosen to minimise the number of demanding amino acids (in terms of coupling, Fmoc removal) in each fragment that are expected to hamper the overall synthetic process. Thus, the hydrophobic amino acids as well as Arg(Pbf) were strategically spread over multiple fragments rather than having them congested in one fragment. This study shows how a peptide that shows big challenges in the synthesis using the common stepwise elongation methodology can be synthesised with an acceptable purity. It also emphasises that choosing the right fragment with certain amino acid constituents is key for a successful synthesis. It is worth highlighting that lower amounts of reagents were required to synthesise the final peptide with an identical purity to that obtained by the automatic synthesiser. 相似文献
75.
Magdalena Witek Luca Pietro Casacci Francesca Barbero Dario Patricelli Marco Sala Simone Bossi Massimo Maffei Michal Woyciechowski Emilio Balletto Simona Bonelli 《Biological journal of the Linnean Society. Linnean Society of London》2013,109(3):699-709
Myrmica ant colonies host numerous insect species, including the larvae of Maculinea butterflies and Microdon myrmicae hoverflies. Little is known about the interspecific relationships among these social parasites and their host ants occurring in sympatric populations. We investigated communities of social parasites to assess the strategies allowing them to share the same pool of resources (i.e. Myrmica colonies). The present study was carried out at five sites inhabited by different social parasite communities, each comprising varying proportions of Maculinea teleius, Maculinea nausithous, Maculinea alcon, and Microdon myrmicae. We investigated their spatial distributions, host segregation, the degree of chemical similarity between social parasites and hosts, and temporal overlaps in colony resource exploitation. Spatial segregation among social parasites was found in two populations and it arises from microhabitat preferences and biological interactions. Local conditions can drive selection on one social parasite to use a Myrmica host species that is not exploited by other social parasites. Myrmica scabrinodis and Myrmica rubra nests infested by larvae of two social parasite species were found and the most common co‐occurrence was between Ma. teleius and Mi. myrmicae. The successful coexistence of these two species derives from their exploitation of the host colony resources at different times of the year. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, 109 , 699–709. 相似文献
76.
Paula Costa-Urrutia Simona Sanvito Nelva Victoria-Cota Luis Enríquez-Paredes Diane Gendron 《PloS one》2013,8(3)
Population differentiation in environments without well-defined geographical barriers represents a challenge for wildlife management. Based on a comprehensive database of individual sighting records (1988–2009) of blue whales from the winter/calving Gulf of California, we assessed the fine-scale genetic and spatial structure of the population using individual-based approaches. Skin samples of 187 individuals were analyzed for nine microsatellite loci. A single population with no divergence among years and months and no isolation by distance (Rxy = 0.1–0.001, p>0.05) were found. We ran two Bayesian clustering methods using Structure and Geneland softwares in two different ways: 1) a general analysis including all individuals in which a single cluster was identified with both softwares; 2) a specific analysis of females only in which two main clusters (Loreto Bay and northern areas, and San Jose-La Paz Bay area) were revealed by Geneland program. This study provides information indicating that blue whales wintering in the Gulf of California are part of a single population unit and showed a fine-scale structure among females, possibly associated with their high site fidelity, particularly when attending calves. It is likely that the loss of genetic variation is minimized by male mediated gene flow, which may reduce the genetic drift effect. Opportunities for kin selection may also influence calf survival and, in consequence, have a positive impact on population demography in this small and endangered population. 相似文献
77.
Usein CR Palade AM Popovici N Tatu-Chitoiu D Ciontea S Damian M 《Roumanian archives of microbiology and immunology》2006,65(3-4):100-104
Bacteremia is the principal way of dissemination of local infections to distant organs. Escherichia coli bacteremia is almost always clinically significant, suggesting an increased risk of developing sepsis syndrome. Fifty-one E. coli bloodstream human isolates were analyzed using PCR technique for several molecular markers associated with extraintestinal virulence, and their phylogenetic group assignment, taking into account the link between the phylogenetic background and the intrinsic virulence of this species. Sixteen virulence genotypes have been identified, the majority of the blood isolates carrying the association of two genes. The genes encoding type 1 fimbria and aerobactin had the highest prevalence. As a confirmation of other studies, the strains assigned to E. coli phylogenetic group B2 exhibited the highest concentration of virulence genes, and represented almost half of the clinical blood isolates. The multifactorial virulence of E. coli strains isolated from invasive infections reflects a phylogenetic inheritance, and supports the concept of ExPEC pathotype as a subset of E. coli population involved in human infectious diseases. The surveillance of geographical variation of E. coli pathogenic clones is useful for epidemiological analysis. 相似文献
78.
Simona Pedrotti Pamela Bielli Maria Paola Paronetto Fabiola Ciccosanti Gian Maria Fimia Stefan Stamm James L Manley Claudio Sette 《The EMBO journal》2010,29(7):1235-1247
Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by loss of motor neurons in patients with null mutations in the SMN1 gene. An almost identical SMN2 gene is unable to compensate for this deficiency because a single C‐to‐T transition at position +6 in exon‐7 causes skipping of the exon by a mechanism not yet fully elucidated. We observed that the C‐to‐T transition in SMN2 creates a putative binding site for the RNA‐binding protein Sam68. RNA pull‐down assays and UV‐crosslink experiments showed that Sam68 binds to this sequence. In vivo splicing assays showed that Sam68 triggers SMN2 exon‐7 skipping. Moreover, mutations in the Sam68‐binding site of SMN2 or in the RNA‐binding domain of Sam68 completely abrogated its effect on exon‐7 skipping. Retroviral infection of dominant‐negative mutants of Sam68 that interfere with its RNA‐binding activity, or with its binding to the splicing repressor hnRNP A1, enhanced exon‐7 inclusion in endogenous SMN2 and rescued SMN protein expression in fibroblasts of SMA patients. Our results thus indicate that Sam68 is a novel crucial regulator of SMN2 splicing. 相似文献
79.
80.