全文获取类型
收费全文 | 3209篇 |
免费 | 220篇 |
国内免费 | 1篇 |
出版年
2023年 | 15篇 |
2022年 | 24篇 |
2021年 | 68篇 |
2020年 | 57篇 |
2019年 | 67篇 |
2018年 | 72篇 |
2017年 | 69篇 |
2016年 | 106篇 |
2015年 | 136篇 |
2014年 | 178篇 |
2013年 | 205篇 |
2012年 | 238篇 |
2011年 | 227篇 |
2010年 | 130篇 |
2009年 | 149篇 |
2008年 | 194篇 |
2007年 | 189篇 |
2006年 | 196篇 |
2005年 | 154篇 |
2004年 | 168篇 |
2003年 | 152篇 |
2002年 | 144篇 |
2001年 | 25篇 |
2000年 | 18篇 |
1999年 | 31篇 |
1998年 | 35篇 |
1997年 | 24篇 |
1996年 | 22篇 |
1995年 | 22篇 |
1994年 | 19篇 |
1993年 | 28篇 |
1992年 | 22篇 |
1991年 | 13篇 |
1990年 | 26篇 |
1989年 | 23篇 |
1988年 | 15篇 |
1987年 | 13篇 |
1986年 | 16篇 |
1985年 | 10篇 |
1984年 | 10篇 |
1983年 | 10篇 |
1982年 | 22篇 |
1981年 | 13篇 |
1980年 | 17篇 |
1979年 | 6篇 |
1978年 | 5篇 |
1977年 | 6篇 |
1976年 | 7篇 |
1975年 | 5篇 |
1973年 | 4篇 |
排序方式: 共有3430条查询结果,搜索用时 406 毫秒
991.
Viviana Dalamón M. Florencia Wernert Vanesa Lotersztein Patricio O. Craig Raúl Reynoso Diamante María E. Barteik Carlos Curet Bibiana Paoli Enrique Mansilla Ana Belén Elgoyhen 《Molecular biology reports》2013,40(12):6945-6955
This paper presents a mutation as well as a genotype–phenotype analysis of the GJB2 and GJB6 genes in 476 samples from non-syndromic unrelated Argentinean deaf patients (104 familial and 372 sporadic cases). Most of them were of prelingual onset (82 %) and 27 % were cochlear implanted. Variation of sequences was detected in 171 of the 474 patients (36 %). Overall, 43 different sequence variations were identified in GJB2 and GJB6. Four of them are reported for the first time in GJB2: c.233dupG, p.Ala78Ser, p.Val190Asp and p.Cys211Tyr. Mutations in GJB6 were detected in 3 % of patients [nine del(GJB6-D13S1830) and three del(GJB6-D13S1854)]. Of the 43 different variations identified in GJB2, 6 were polymorphisms and of the others, 10 (27 %) were truncating and 27 (73 %) were nontruncating. Patients with two truncating mutations had significantly worse hearing impairment than all other groups. Moderate phenotypes were observed in a group of patients carrying biallelic mutations (23 %). This work shows the high prevalence of GJB2 mutations in the Argentinean population and presents an analysis of moderate phenotypes in our cohort. 相似文献
992.
Leonardo O. Alvarado-Cárdenas Enrique Martínez-Meyer Teresa P. Feria Luis E. Eguiarte Héctor M. Hernández Guy Midgley Mark E. Olson 《Annals of botany》2013,111(6):1125-1138
Background and Aims
Convergent evolution is invoked to explain similarity between unrelated organisms in similar environments, but most evaluations of convergence analyse similarity of organismal attributes rather than of the environment. This study focuses on the globular succulent plants of the Americas, the cacti, and their counterparts in Africa in the ice-plant, spurge and milkweed families. Though often held up as paragons of convergent morphological evolution, the environmental similarity of these plants has remained largely unexamined from a quantitative perspective.Methods
Five hotspots (centres of high species diversity of globular succulents) were selected, two in Mexico and three in South Africa. Their environments were compared using niche modelling tools, randomization tests of niche similarity and multivariate analyses to test for environmental similarity.Key Results
Although the sites selected have ‘similar’ but unrelated life forms, almost all our results highlighted more climate differences than similarities between the hotspots. Interprediction of niches within and between continents, a niche equivalence test, and MANOVA results showed significant differences. In contrast, a niche similarity test showed that the comparisons of Cuatrociénegas–Richtersveld, Huizache–Knersvlakte and Huizache–Richtersveld were similar.Conclusions
Differences in rainfall and temperature regimes and the potential effect of edaphic factors may be involved in the differences between the hotspots. In addition, differences in structure, morphology and physiology of the globular succulents may coincide with some of the climatic dissimilarities; i.e. given convergence as the evolution of similar morphologies under similar conditions, then it may be that differing environments diagnose inconspicuous morphological differences. Moreover, although fine-scale differences between sites were found, a coarser perspective shows that these sites are clearly similar as drylands with relatively moderate drought and mild temperatures, illustrating how all studies of convergence must address the issue of how similar two entities must be before they are considered convergent. 相似文献993.
Verónica Fasulo ZhiQiang Zhang Juan G. Chediack Fabricio D. Cid William H. Karasov Enrique Caviedes-Vidal 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2013,183(2):289-296
Water-soluble nutrients are absorbed by the small intestine via transcellular and paracellular processes. The capacity for paracellular absorption seems greater in fliers than in nonfliers, although that conclusion rests mainly on a comparison of flying birds and nonflying mammals because only two frugivorous bat species have been studied. Furthermore, the bats studied so far were relatively large (>85 g, compared with most bat species which are <20 g) and were not insectivores (like about 70 % of bat species). We studied the small (11 g) insectivorous bat Tadarida brasiliensis and tested the prediction that the capacity for paracellular absorption would be as high as in the other bat and avian species studied so far, well above that in terrestrial, nonflying mammals. Using standard pharmacokinetic technique, we measured the extent of absorption (fractional absorption = f) of inert carbohydrate probes: L-arabinose (MM = 150.13) absorbed exclusively by paracellular route and 3OMD-glucose (MM = 194) absorbed both paracellularly and transcellularly. As predicted, the capacity of paracellular absorption in this insectivorous bat was high (L-arabinose f = 1.03 ± 0.14) as in other frugivorous bats and small birds. Absorption of 3OMD-glucose was also complete (f = 1.09 ± 0.17), but >80 % was accounted for by paracellular absorption. We conclude that passive paracellular absorption of molecules of the size of amino acids and glucose is extensive in this bat and, generally in bats, significantly higher than that in nonflying mammals, although the exact extent can be somewhat lower or higher depending on molecule size, polarity and charge. 相似文献
994.
Tamás Papp Árpád Csernetics Gábor Nagy Ottó Bencsik Enrique A. Iturriaga Arturo P. Eslava Csaba Vágvölgyi 《Applied microbiology and biotechnology》2013,97(11):4937-4950
Canthaxanthin is a natural diketo derivative of β-carotene primarily used by the food and feed industries. Mucor circinelloides is a β-carotene-accumulating zygomycete fungus and one of the model organisms to study the carotenoid biosynthesis in fungi. In this study, the β-carotene ketolase gene (crtW) of the marine bacterium Paracoccus sp. N81106 fused with fungal promoter and terminator regions was integrated into the M. circinelloides genome to construct stable canthaxanthin-producing strains. Different transformation methods including polyethylene glycol-mediated transformation with linear DNA fragments, restriction enzyme-mediated integration and Agrobacterium tumefaciens-mediated transformation were tested to integrate the crtW gene into the Mucor genome. Mitotic stability, site of integration and copy number of the transferred genes were analysed in the transformants, and several stable strains containing the crtW gene in high copy number were isolated. Carotenoid composition of selected transformants and effect of culturing conditions, such as temperature, carbon sources and application of certain additives in the culturing media, on their carotenoid content were analysed. Canthaxanthin-producing transformants were able to survive at higher growth temperature than the untransformed strain, maybe due to the effect of canthaxanthin on the membrane fluidity and integrity. With the application of glucose, trehalose, dihydroxyacetone and l-aspartic acid as sole carbon sources in minimal medium, the crtW-expressing M. circinelloides strain, MS12+pCA8lf/1, produced more than 200 μg/g (dry mass) of canthaxanthin. 相似文献
995.
Epidemiology studies revealed the connection between several types of cancer and type 2 diabetes (T2D) and suggested that T2D is both a symptom and a risk factor of pancreatic cancer. High level of circulating insulin (hyperinsulinemia) in obesity has been implicated in promoting aggressive types of cancers. Insulin resistance, a symptom of T2D, pressures pancreatic β-cells to increase insulin secretion, leading to hyperinsulinemia, which in turn leads to a gradual loss of functional β-cell mass, thus indicating a fine balance and interplay between β-cell function and mass. While the mechanisms of these connections are unclear, the mTORC1-Akt signaling pathway has been implicated in controlling β-cell function and mass, and in mediating the link of cancer and T2D. However, incomplete understating of how the pathway is regulated and how it integrates body metabolism has hindered its efficacy as a clinical target. The IQ motif containing GTPase activating protein 1 (IQGAP1)-Exocyst axis is a growth factor- and nutrient-sensor that couples cell growth and division. Here we discuss how IQGAP1-Exocyst, through differential interactions with Rho-type of small guanosine triphosphatases (GTPases), acts as a rheostat that modulates the mTORC1-Akt and MAPK signals, and integrates β-cell function and mass with insulin signaling, thus providing a molecular mechanism for cancer initiation in diabetes. Delineating this regulatory pathway may have the potential of contributing to optimizing the efficacy and selectivity of future therapies for cancer and diabetes. 相似文献
996.
As part of population dynamics studies of the South American fur seal (Arctophoca australis gracilis) rookery at Punta Weather in Guafo Island (43°36'S, 74°43’W), the causes and extent of pup mortality were monitored. During four breeding seasons, daily counts of live and dead pups were carried out to determine pup production and pup mortality. Dead pups were retrieved from the rookery to perform necropsies. The mean pup production was 1,735.5 ± 336 pups and the mean pup mortality up to 12 wk old was 6.0%± 2.6%. The major causes of death were enteritis with microscopic lesions of bacteremia (28.4%), starvation (23.5%), drowning (21%), trauma (19.8%), and stillbirths (2.5%). Enteritis with microscopic lesions of bacteremia, and starvation had higher incidence during January (beginning and middle of the breeding season) while most trauma and drowning occurred during February (end of the breeding season). In the 2006–2007 breeding season there was an increase in mortality due to starvation and trauma. Most pup deaths at Guafo Island are generated by extrinsic factors; therefore, additional studies that assess the impact of environmental changes and fishing activities, are needed in order to determine the exact causes of the decline of this species along Chilean coasts. 相似文献
997.
998.
Jose A. Estevez Tomás Landete-Castillejos Andrés J. García Enrique Gaspar-López Francisco Ceacero Laureano Gallego 《Acta theriologica》2011,56(4):323-328
Climate variability greatly affects animals through direct and indirect effects. Animals with slow reproductive adaptation to ecological changes such as large mammals are likely to have evolved mechanisms to anticipate early such impacts of climate variability on the environment. One of the adaptive mechanisms between reproductive costs and benefits in mammals affects parental investment through biases in sex ratio. Deer might be likely to show an early detection of climate variability because conception takes place in early autumn, but the main raising cost in deer concerns lactation, which takes place at the end of the following spring. The aim of this paper is to assess whether there is a relationship between global indices of climate variability such as El Niño-Southern Oscillation (ENSO) and sex ratio of a captive population of deer. Results showed that there was a negative correlation (r=?0.65) between sex ratio and ENSO indices between 1996 and 2008. El Niño enhances drier conditions during the summer in the Iberia Peninsula, which in turn favours a female bias. Results also suggest that the mechanism of early detection of climate variability exerts a strong effect on female reproductive physiology because the long-term stability of food resources in our setting has not markedly reduced it. 相似文献
999.
An understanding of the interplay between structure and energetics is crucial for the optimization of modern protein engineering techniques. In this context, the study of natural isoforms is a subject of major interest, as it provides the scenario for analyzing mutations that have endured during biological evolution. In this study, we performed a comparative analysis of the ligand-recognition and homodimerization energetics of bovine β-lactoglobulin variants A (βlgA) and B (βlgB). These variants differ by only two amino-acid substitutions: 64th (Asp(A) → Gly(B)), which is fully exposed to the solvent, and 118th (Val(A) → Ala(B)), immersed in the hydrophobic core of the protein. Calorimetric measurements revealed significant enthalpic and entropic differences between the isoforms in both binding processes. A structural comparison suggests that a variation in the conformation of the loop C-D, induced by mutation Asp/Gly, could be responsible for the differences in ligand-binding energetics. While recognition of lauric acid was entropically driven, recognition of sodium dodecyl sulfate was both entropically and enthalpically driven, confirming the key role of the ligand polar moiety. Because of a more favorable enthalpy, the dimerization equilibrium constant of βlgB was larger than that of βlgA at room temperature, while the two dimers became similarly stable at 35 °C. The isoforms exchanged the same number of structural water molecules and protons and shared similar stereochemistry at the dimer interface. MD simulations revealed that the subunits of both variants become more flexible upon dimer formation. It is hypothesized that a larger increase of βlgA mobility could account for the dimerization energetic differences observed. 相似文献
1000.
Morphogenesis of plant cells is tantamount to the shaping of the stiff cell wall that surrounds them. To this end, these cells integrate two concomitant processes: 1), deposition of new material into the existing wall, and 2), mechanical deformation of this material by the turgor pressure. However, due to uncertainty regarding the mechanisms that coordinate these processes, existing models typically adopt a limiting case in which either one or the other dictates morphogenesis. In this report, we formulate a simple mechanism in pollen tubes by which deposition causes turnover of cell wall cross-links, thereby facilitating mechanical deformation. Accordingly, deposition and mechanics are coupled and are both integral aspects of the morphogenetic process. Among the key experimental qualifications of this model are: its ability to precisely reproduce the morphologies of pollen tubes; its prediction of the growth oscillations exhibited by rapidly growing pollen tubes; and its prediction of the observed phase relationships between variables such as wall thickness, cell morphology, and growth rate within oscillatory cells. In short, the model captures the rich phenomenology of pollen tube morphogenesis and has implications for other plant cell types. 相似文献