全文获取类型
收费全文 | 1300篇 |
免费 | 152篇 |
专业分类
1452篇 |
出版年
2023年 | 6篇 |
2022年 | 14篇 |
2021年 | 32篇 |
2020年 | 10篇 |
2019年 | 12篇 |
2018年 | 17篇 |
2017年 | 14篇 |
2016年 | 29篇 |
2015年 | 59篇 |
2014年 | 61篇 |
2013年 | 60篇 |
2012年 | 89篇 |
2011年 | 112篇 |
2010年 | 57篇 |
2009年 | 53篇 |
2008年 | 78篇 |
2007年 | 75篇 |
2006年 | 66篇 |
2005年 | 73篇 |
2004年 | 67篇 |
2003年 | 68篇 |
2002年 | 61篇 |
2001年 | 21篇 |
2000年 | 16篇 |
1999年 | 17篇 |
1998年 | 21篇 |
1997年 | 10篇 |
1996年 | 10篇 |
1995年 | 7篇 |
1994年 | 8篇 |
1993年 | 10篇 |
1992年 | 8篇 |
1991年 | 10篇 |
1990年 | 13篇 |
1989年 | 11篇 |
1988年 | 10篇 |
1987年 | 7篇 |
1986年 | 10篇 |
1984年 | 8篇 |
1983年 | 6篇 |
1982年 | 13篇 |
1981年 | 13篇 |
1980年 | 8篇 |
1979年 | 9篇 |
1978年 | 8篇 |
1977年 | 13篇 |
1976年 | 6篇 |
1975年 | 6篇 |
1974年 | 15篇 |
1973年 | 7篇 |
排序方式: 共有1452条查询结果,搜索用时 15 毫秒
81.
Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia
Moreno-De-Luca D;SGENE Consortium Mulle JG;Simons Simplex Collection Genetics Consortium Kaminsky EB Sanders SJ;GeneSTAR Myers SM Adam MP Pakula AT Eisenhauer NJ Uhas K Weik L Guy L Care ME Morel CF Boni C Salbert BA Chandrareddy A Demmer LA Chow EW Surti U Aradhya S Pickering DL Golden DM Sanger WG Aston E Brothman AR Gliem TJ Thorland EC Ackley T Iyer R Huang S Barber JC Crolla JA Warren ST Martin CL Ledbetter DH 《American journal of human genetics》2010,87(5):618-630
Autism spectrum disorders (ASD) and schizophrenia are neurodevelopmental disorders for which recent evidence indicates an important etiologic role for rare copy number variants (CNVs) and suggests common genetic mechanisms. We performed cytogenomic array analysis in a discovery sample of patients with neurodevelopmental disorders referred for clinical testing. We detected a recurrent 1.4 Mb deletion at 17q12, which harbors HNF1B, the gene responsible for renal cysts and diabetes syndrome (RCAD), in 18/15,749 patients, including several with ASD, but 0/4,519 controls. We identified additional shared phenotypic features among nine patients available for clinical assessment, including macrocephaly, characteristic facial features, renal anomalies, and neurocognitive impairments. In a large follow-up sample, the same deletion was identified in 2/1,182 ASD/neurocognitive impairment and in 4/6,340 schizophrenia patients, but in 0/47,929 controls (corrected p = 7.37 × 10−5). These data demonstrate that deletion 17q12 is a recurrent, pathogenic CNV that confers a very high risk for ASD and schizophrenia and show that one or more of the 15 genes in the deleted interval is dosage sensitive and essential for normal brain development and function. In addition, the phenotypic features of patients with this CNV are consistent with a contiguous gene syndrome that extends beyond RCAD, which is caused by HNF1B mutations only. 相似文献
82.
Jane Elith Catherine H. Graham Robert P. Anderson Miroslav Dudík Simon Ferrier Antoine Guisan Robert J. Hijmans Falk Huettmann John R. Leathwick Anthony Lehmann Jin Li Lucia G. Lohmann Bette A. Loiselle Glenn Manion Craig Moritz Miguel Nakamura Yoshinori Nakazawa Jacob McC. M. Overton A. Townsend Peterson Steven J. Phillips Karen Richardson Ricardo Scachetti-Pereira Robert E. Schapire Jorge Soberón Stephen Williams Mary S. Wisz Niklaus E. Zimmermann 《Ecography》2006,29(2):129-151
Prediction of species' distributions is central to diverse applications in ecology, evolution and conservation science. There is increasing electronic access to vast sets of occurrence records in museums and herbaria, yet little effective guidance on how best to use this information in the context of numerous approaches for modelling distributions. To meet this need, we compared 16 modelling methods over 226 species from 6 regions of the world, creating the most comprehensive set of model comparisons to date. We used presence-only data to fit models, and independent presence-absence data to evaluate the predictions. Along with well-established modelling methods such as generalised additive models and GARP and BIOCLIM, we explored methods that either have been developed recently or have rarely been applied to modelling species' distributions. These include machine-learning methods and community models, both of which have features that may make them particularly well suited to noisy or sparse information, as is typical of species' occurrence data. Presence-only data were effective for modelling species' distributions for many species and regions. The novel methods consistently outperformed more established methods. The results of our analysis are promising for the use of data from museums and herbaria, especially as methods suited to the noise inherent in such data improve. 相似文献
83.
Stoichiometry of soil enzyme activity at global scale 总被引:27,自引:0,他引:27
Sinsabaugh RL Lauber CL Weintraub MN Ahmed B Allison SD Crenshaw C Contosta AR Cusack D Frey S Gallo ME Gartner TB Hobbie SE Holland K Keeler BL Powers JS Stursova M Takacs-Vesbach C Waldrop MP Wallenstein MD Zak DR Zeglin LH 《Ecology letters》2008,11(11):1252-1264
Extracellular enzymes are the proximate agents of organic matter decomposition and measures of these activities can be used as indicators of microbial nutrient demand. We conducted a global-scale meta-analysis of the seven-most widely measured soil enzyme activities, using data from 40 ecosystems. The activities of beta-1,4-glucosidase, cellobiohydrolase, beta-1,4-N-acetylglucosaminidase and phosphatase g(-1) soil increased with organic matter concentration; leucine aminopeptidase, phenol oxidase and peroxidase activities showed no relationship. All activities were significantly related to soil pH. Specific activities, i.e. activity g(-1) soil organic matter, also varied in relation to soil pH for all enzymes. Relationships with mean annual temperature (MAT) and precipitation (MAP) were generally weak. For hydrolases, ratios of specific C, N and P acquisition activities converged on 1 : 1 : 1 but across ecosystems, the ratio of C : P acquisition was inversely related to MAP and MAT while the ratio of C : N acquisition increased with MAP. Oxidative activities were more variable than hydrolytic activities and increased with soil pH. Our analyses indicate that the enzymatic potential for hydrolyzing the labile components of soil organic matter is tied to substrate availability, soil pH and the stoichiometry of microbial nutrient demand. The enzymatic potential for oxidizing the recalcitrant fractions of soil organic material, which is a proximate control on soil organic matter accumulation, is most strongly related to soil pH. These trends provide insight into the biogeochemical processes that create global patterns in ecological stoichiometry and organic matter storage. 相似文献
84.
85.
Swoap SJ Overton JM Garber G 《American journal of physiology. Regulatory, integrative and comparative physiology》2004,287(2):R391-R396
Ambient air temperatures (T(a)) of <6 degrees C or >29 degrees C have been shown to induce large changes in arterial blood pressure and heart rate in homeotherms. The present study was designed to investigate whether small incremental changes in T(a), such as those found in typical laboratory settings, would have an impact on blood pressure and other cardiovascular parameters in mice and rats. We predicted that small decreases in T(a) would impact the cardiovascular parameters of mice more than rats due to the increased thermogenic demands resulting from a greater surface area-to-volume ratio in mice relative to rats. Cardiovascular parameters were measured with radiotelemetry in mice and rats that were housed in temperature-controlled environments. The animals were exposed to different T(a) every 72 h, beginning at 30 degrees C and incrementally decreasing by 4 degrees C at each time interval to 18 degrees C and then incrementally increasing back up to 30 degrees C. As T(a) decreased, mean blood pressure, heart rate, and pulse pressure increased significantly for both mice (1.6 mmHg/ degrees C, 14.4 beats.min(-1). degrees C(-1), and 0.8 mmHg/ degrees C, respectively) and rats (1.2 mmHg/ degrees C, 8.1 beats.min(-1). degrees C(-1), and 0.8 mmHg/ degrees C, respectively). Thus small changes in T(a) significantly impact the cardiovascular parameters of both rats and mice, with mice demonstrating a greater sensitivity to these T(a) changes. 相似文献
86.
Real-time three-dimensional imaging of lipid signal transduction: apical membrane insertion of epithelial Na(+) channels 总被引:2,自引:0,他引:2
Blazer-Yost BL Vahle JC Byars JM Bacallao RL 《American journal of physiology. Cell physiology》2004,287(6):C1569-C1576
In the distal tubule, Na+ resorption is mediated by epithelial Na+ channels (ENaC). Hormones such as aldosterone, vasopressin, and insulin modulate ENaC membrane targeting, assembly, and/or kinetic activity, thereby regulating salt and water homeostasis. Insulin binds to a receptor on the basal membrane to initiate a signal transduction cascade that rapidly results in an increase in apical membrane ENaC. Current models of this signaling pathway envision diffusion of signaling intermediates from the basal to the apical membrane. This necessitates diffusion of several high-molecular-weight signaling elements across a three-dimensional space. Transduction of the insulin signal involves the phosphoinositide pathway, but how and where this lipid-based signaling pathway controls ENaC activity is not known. We used tagged channels, biosensor lipid probes, and intravital imaging to investigate the role of lipids in insulin-stimulated Na+ flux. Insulin-stimulated delivery of intracellular ENaC to apical membranes was concurrent with plasma membrane-limited changes in lipid composition. Notably, in response to insulin, phosphatidylinositol 3,4,5-trisphosphate (PIP3) formed in the basolateral membrane, rapidly diffused within the bilayer, and crossed the tight junction to enter the apical membrane. This novel signaling pathway takes advantage of the fact that the lipids of the plasma membrane's inner leaflet are not constrained by the tight junction. Therefore, diffusion of PIP3 as a signal transduction intermediate occurs within a planar surface, thus facilitating swift responses and confining and controlling the signaling pathway. phosphatidylinositol 3,4,5-trisphosphate; insulin-stimulated Na+ transport; metabolic syndrome; real-time confocal imaging 相似文献
87.
Helal CJ Sanner MA Cooper CB Gant T Adam M Lucas JC Kang Z Kupchinsky S Ahlijanian MK Tate B Menniti FS Kelly K Peterson M 《Bioorganic & medicinal chemistry letters》2004,14(22):5521-5525
High-throughput screening with cyclin-dependent kinase 5 (cdk5)/p25 led to the discovery of N-(5-isopropyl-thiazol-2-yl)isobutyramide (1). This compound is an equipotent inhibitor of cdk5 and cyclin-dependent kinase 2 (cdk2)/cyclin E (IC(50)=ca. 320nM). Parallel and directed synthesis techniques were utilized to explore the SAR of this series. Up to 60-fold improvements in potency at cdk5 and 12-fold selectivity over cdk2 were achieved. 相似文献
88.
Jacobs BF 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2004,359(1450):1573-1583
Fossil plants provide data on climate, community composition and structure, all of which are relevant to the definition and recognition of biomes. Macrofossils reflect local vegetation, whereas pollen assemblages sample a larger area. The earliest solid evidence for angiosperm tropical rainforest in Africa is based primarily on Late Eocene to Late Oligocene (ca. 39-26 Myr ago) pollen assemblages from Cameroon, which are rich in forest families. Plant macrofossil assemblages from elsewhere in interior Africa for this time interval are rare, but new work at Chilga in the northwestern Ethiopian Highlands documents forest communities at 28 Myr ago. Initial results indicate botanical affinities with lowland West African forest. The earliest known woodland community in tropical Africa is dated at 46 Myr ago in northern Tanzania, as documented by leaves and fruits from lake deposits. The community around the lake was dominated by caesalpinioid legumes, but included Acacia, for which this, to my knowledge, is the earliest record. This community is structurally similar to modern miombo, although it is different at the generic level. The grass-dominated savannah biome began to expand in the Middle Miocene (16 Myr ago), and became widespread in the Late Miocene (ca. 8 Myr ago), as documented by pollen and carbon isotopes from both West and East Africa. 相似文献
89.
Molecular phylogenetic relationships based on mitochondrial and nuclear gene sequences for the Todies (Todus, Todidae) of the Caribbean 总被引:2,自引:0,他引:2
We used mitochondrial/nuclear gene sequence analyses to determine the historical relationships of the endemic species of Todus (Aves: Todidae) from the Caribbean. We collected 1920-bp of nucleotide sequence data from the mitochondrial genes cytochrome b, ATPase 6, ATPase 8, and 591-bp of the single-copy nuclear gene c-mos for all Todus species and representatives of their outgroup taxa (Hylomanes, Barypthengus, Chloroceryle, Ceryle, and Galbula) to reconstruct the evolutionary history (via parsimony and maximum likelihood) of the five Todus species. The substitution rates among the mitochondrial genes were found to be much higher than the substitution rate for the c-mos gene, consequently resulting in higher substitutional saturation for the mitochondrial genes. When we applied weighting schemes to account for the variance in substitutional heterogeneity among the genes then parsimony and likelihood analyses both demonstrate that the genus Todus is monophyletic and closer to the Hylomanes and Barypthengus genera than the Chloroceryle and Ceryle genera. The mitochondrial-gene trees and nuclear-gene trees both show similar results, thus providing support for the relationships among the taxa from loci within two independently evolving genomes. The nuclear gene c-mos was found, therefore, to be a viable nuclear gene candidate for resolving intermediate and deep divergences. 相似文献
90.
Immunotherapies for cancer offer attractive alternatives to conventional therapies although human anti-globulin antibody (HAGA) against the antibody (Ab) administered to the patient can be an obstacle to repeated treatment. Monoclonal antibodies (mAb), whether foreign or human in origin, have been used safely in patients for two decades. Adverse events have not proven to be significant clinical obstacles, although alterations of pharmacokinetic behavior of subsequently administered Ab can lead to less effective therapy. Not only is HAGA safe, but it can be associated with beneficial immunity in patients. Studies have shown that some patients have unexpectedly prolonged survival associated with HAGA. In our own non-Hodgkin's lymphoma (NHL) patients treated with mouse Lym-1 anti-lymphoma mAb, a high human anti-mouse Ab (HAMA) titer was associated with increased survival. The possible mechanisms linking HAMA responses to survival are likely related to Ab generated against the idiotopes of the administered Ab. An induced immune cascade in these patients, including anti-idiotypic Ab (Ab2) and cytotoxic Ab1' or Ab3 probably contributed to survival. In summary, HAGA should not a priori preclude the therapeutic use of Ab for cancer. 相似文献