全文获取类型
收费全文 | 3167篇 |
免费 | 263篇 |
国内免费 | 2篇 |
专业分类
3432篇 |
出版年
2023年 | 12篇 |
2022年 | 43篇 |
2021年 | 65篇 |
2020年 | 34篇 |
2019年 | 49篇 |
2018年 | 79篇 |
2017年 | 54篇 |
2016年 | 119篇 |
2015年 | 174篇 |
2014年 | 182篇 |
2013年 | 208篇 |
2012年 | 289篇 |
2011年 | 267篇 |
2010年 | 167篇 |
2009年 | 157篇 |
2008年 | 188篇 |
2007年 | 209篇 |
2006年 | 167篇 |
2005年 | 164篇 |
2004年 | 130篇 |
2003年 | 122篇 |
2002年 | 132篇 |
2001年 | 26篇 |
2000年 | 11篇 |
1999年 | 28篇 |
1998年 | 28篇 |
1997年 | 28篇 |
1996年 | 15篇 |
1995年 | 12篇 |
1994年 | 17篇 |
1993年 | 17篇 |
1992年 | 19篇 |
1991年 | 15篇 |
1990年 | 10篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1985年 | 16篇 |
1984年 | 10篇 |
1983年 | 7篇 |
1982年 | 12篇 |
1981年 | 6篇 |
1980年 | 10篇 |
1978年 | 5篇 |
1975年 | 5篇 |
1974年 | 7篇 |
1971年 | 6篇 |
1957年 | 5篇 |
1953年 | 4篇 |
1946年 | 4篇 |
排序方式: 共有3432条查询结果,搜索用时 15 毫秒
91.
Erica S. Rinella Yongzhao Shao Lauren Yackowski Sreemanta Pramanik Ruth Oratz Freya Schnabel Saurav Guha Charles LeDuc Christopher L. Campbell Susan D. Klugman Mary Beth Terry Ruby T. Senie Irene L. Andrulis Mary Daly Esther M. John Daniel Roses Wendy K. Chung Harry Ostrer 《Human genetics》2013,132(5):523-536
The ability to establish genetic risk models is critical for early identification and optimal treatment of breast cancer. For such a model to gain clinical utility, more variants must be identified beyond those discovered in previous genome-wide association studies (GWAS). This is especially true for women at high risk because of family history, but without BRCA1/2 mutations. This study incorporates three datasets in a GWAS analysis of women with Ashkenazi Jewish (AJ) homogeneous ancestry. Two independent discovery cohorts comprised 239 and 238 AJ women with invasive breast cancer or preinvasive ductal carcinoma in situ and strong family histories of breast cancer, but lacking the three BRCA1/2 founder mutations, along with 294 and 230 AJ controls, respectively. An independent, third cohort of 203 AJ cases with familial breast cancer history and 263 healthy controls of AJ women was used for validation. A total of 19 SNPs were identified as associated with familial breast cancer risk in AJ women. Among these SNPs, 13 were identified from a panel of 109 discovery SNPs, including an FGFR2 haplotype. In addition, six previously identified breast cancer GWAS SNPs were confirmed in this population. Seven of the 19 markers were significant in a multivariate predictive model of familial breast cancer in AJ women, three novel SNPs [rs17663555(5q13.2), rs566164(6q21), and rs11075884(16q22.2)], the FGFR2 haplotype, and three previously published SNPs [rs13387042(2q35), rs2046210(ESR1), and rs3112612(TOX3)], yielding moderate predictive power with an area under the curve (AUC) of the ROC (receiver-operator characteristic curve) of 0.74. Population-specific genetic variants in addition to variants shared with populations of European ancestry may improve breast cancer risk prediction among AJ women from high-risk families without founder BRCA1/2 mutations. 相似文献
92.
Daniel Hernández-Sotelo Rubén García-Aguilar Yaneth Castro-Coronel Jonathan J. Magaña Marco Antonio Leyva-Vazquez Luz del Carmen Alarcón-Romero Esther López-Bayghen Berenice Illades-Aguiar 《Molecular biology reports》2013,40(7):4275-4280
Abnormal methylation is related to cancer development. Since DNMT3B is an enzyme that modulates genomic methylation, we hypothesized that genetic variants of the promoter DNMT3B may be associated with an increased risk of developing cervical cancer. Our aim was to investigate the association between ?579GT and 46359CT polymorphisms of DNMT3B and cervical cancer, high-grade squamous intraepithelial lesions (HSIL), and low-grade squamous intraepithelial lesions (LSIL). Samples from 200 healthy women and 130 women with squamous intraepithelial lesions (70 with cervical cancer, 30 with HSIL, and 30 with LSIL) were analyzed. Polymorphism genotyping was performed using PCR and restriction fragment length polymorphism. The ?579GT polymorphism was not associated with cervical cancer, HSIL, or LSIL. The CT genotype of 46359CT polymorphism was significantly associated with cervical cancer risk (OR 8.75, CI 1.27–374.1), whereas the TT genotype was associated with a significantly decreased risk of HSIL (OR 0.66, CI 0.01–0.32) and LSIL (OR 0.11, CI 0.026–0.45). Our results suggest that genotyping the 46359CT polymorphism in DNMT3B may help identify women who are genetically susceptible to cervical cancer development. Additional studies with larger sample sizes are necessary to confirm our findings. 相似文献
93.
Ilary Allodi Laura Casals-Díaz Eva Santos-Nogueira Francisco Gonzalez-Perez Xavier Navarro Esther Udina 《Molecular neurobiology》2013,47(2):770-781
In this study, we screened in vitro the different capabilities of trophic factors with promising effect for enhancing selective regeneration and thus promoting specific reinnervation of target organs after peripheral nerve regeneration. We found that FGF-2 (18 kDa) was the trophic factor that exerted the most selective effect in promoting neurite outgrowth of spinal motoneurons both in terms of elongation and arborization. The mechanism underlying this effect on neuritogenesis seems related to FGF-2 enhancing the interaction between FGFR-1 and PSA-NCAM. The interaction of these two receptors is important during the early stages of neuritogenesis and pathfinding, while integrin alpha7B subunit seems to play a role during neurite stabilization. 相似文献
94.
95.
Eric Allan Wolfgang W. Weisser Markus Fischer Ernst-Detlef Schulze Alexandra Weigelt Christiane Roscher Jussi Baade Romain L. Barnard Holger Beßler Nina Buchmann Anne Ebeling Nico Eisenhauer Christof Engels Alexander J. F. Fergus Gerd Gleixner Marlén Gubsch Stefan Halle Alexandra M. Klein Ilona Kertscher Annely Kuu Markus Lange Xavier Le Roux Sebastian T. Meyer Varvara D. Migunova Alexandru Milcu Pascal A. Niklaus Yvonne Oelmann Esther Pašalić Jana S. Petermann Franck Poly Tanja Rottstock Alexander C. W. Sabais Christoph Scherber Michael Scherer-Lorenzen Stefan Scheu Sibylle Steinbeiss Guido Schwichtenberg Vicky Temperton Teja Tscharntke Winfried Voigt Wolfgang Wilcke Christian Wirth Bernhard Schmid 《Oecologia》2013,173(1):223-237
In order to predict which ecosystem functions are most at risk from biodiversity loss, meta-analyses have generalised results from biodiversity experiments over different sites and ecosystem types. In contrast, comparing the strength of biodiversity effects across a large number of ecosystem processes measured in a single experiment permits more direct comparisons. Here, we present an analysis of 418 separate measures of 38 ecosystem processes. Overall, 45 % of processes were significantly affected by plant species richness, suggesting that, while diversity affects a large number of processes not all respond to biodiversity. We therefore compared the strength of plant diversity effects between different categories of ecosystem processes, grouping processes according to the year of measurement, their biogeochemical cycle, trophic level and compartment (above- or belowground) and according to whether they were measures of biodiversity or other ecosystem processes, biotic or abiotic and static or dynamic. Overall, and for several individual processes, we found that biodiversity effects became stronger over time. Measures of the carbon cycle were also affected more strongly by plant species richness than were the measures associated with the nitrogen cycle. Further, we found greater plant species richness effects on measures of biodiversity than on other processes. The differential effects of plant diversity on the various types of ecosystem processes indicate that future research and political effort should shift from a general debate about whether biodiversity loss impairs ecosystem functions to focussing on the specific functions of interest and ways to preserve them individually or in combination. 相似文献
96.
Jose Itzigsohn Carlos Dore Cabral Esther Hernandez Medina Obed Vazquez 《Ethnic and racial studies》2013,36(2):316-339
This article maps the structure for understanding the Dominican transnational field. By transnational field we refer to a web of linkages that affects the lives of Dominicans in their places of residence in every social field. We find that social boundaries of the nation do not coincide with political ones and the degree of participation in transnational exchanges varies. We suggest that the structure of the transnational social field is better understood by establishing and defining broad and narrow transnational social practices. 相似文献
97.
Samantha A. Spangler Sabine K. Schmitz Josta T. Kevenaar Esther de Graaff Heidi de Wit Jeroen Demmers Ruud F. Toonen Casper C. Hoogenraad 《The Journal of cell biology》2013,201(6):915-928
The presynaptic active zone mediates synaptic vesicle exocytosis, and modulation of its molecular composition is important for many types of synaptic plasticity. Here, we identify synaptic scaffold protein liprin-α2 as a key organizer in this process. We show that liprin-α2 levels were regulated by synaptic activity and the ubiquitin–proteasome system. Furthermore, liprin-α2 organized presynaptic ultrastructure and controlled synaptic output by regulating synaptic vesicle pool size. The presence of liprin-α2 at presynaptic sites did not depend on other active zone scaffolding proteins but was critical for recruitment of several components of the release machinery, including RIM1 and CASK. Fluorescence recovery after photobleaching showed that depletion of liprin-α2 resulted in reduced turnover of RIM1 and CASK at presynaptic terminals, suggesting that liprin-α2 promotes dynamic scaffolding for molecular complexes that facilitate synaptic vesicle release. Therefore, liprin-α2 plays an important role in maintaining active zone dynamics to modulate synaptic efficacy in response to changes in network activity. 相似文献
98.
Capsule Mediterranean Great Tits showed a marked increase in levels of circulating carotenoids during moult and autumn.Aims To study seasonal variation in plasma carotenoid content during a whole annual cycle for Great Tits Parus major inhabiting a Mediterranean woodland.Methods We used a sample of 71 adult male Great Tits captured in NE Spain during a whole year. Data were organized into four seasons (winter, breeding, moult and autumn). We sampled blood to extract plasma. Carotenoid plasma concentrations were analysed by High-performance liquid chromatography (HPLC).Results Lutein and zeaxanthin content varied seasonally, with a marked increase in levels during moult and autumn. Within the moulting period, levels increased gradually as the season progressed. This pattern differed significantly from that previously described in northern European populations, where high values appear mainly in the breeding season. Carotenoid concentrations (lutein: 1.2?±?0.25, zeaxanthin: 0.07?±?0.03?µg mL?1) were also lower than in northern Europe.Conclusion Mediterranean Great Tits show a very different pattern of circulating carotenoids and lower levels than northern European populations. The increasing pattern of carotenoid availability found within the moulting period raises the need to control for the effect of sampling date when analysing data on carotenoid concentrations at different times of year. 相似文献
99.
Esther Leal Begoña Fernández-Durán Maria Josep Agulleiro Marta Conde-Siera Jesús Manuel Míguez José Miguel Cerdá-Reverter 《Hormones and behavior》2013
Dopamine is synthesized from l-dopa and subsequently processed into norepinephrine and epinephrine. Any excess neurotransmitter can be taken up again by the neurons to be broken down enzymatically into DOPAC. The effect of dopamine on mammalian food intake is controversial. Mice unable to synthesize central dopamine die of starvation. However, studies have also shown that central injection of dopamine inhibits food intake. The effect of dopaminergic system in the fish feeding behavior has been scarcely explored. We report that the inclusion of l-dopa in the diets results in the activation of sea bass central dopaminergic system but also in the significant increase of the hypothalamic serotonin levels. Dietary l-dopa induces a decrease of food intake and feed conversion efficiency that drives a decline of all growth parameters tested. No behavioral effects were observed after l-dopa treatment. l-dopa treatment stimulated central expression of NPY and CRF. It suggests that CRF might mediate l-dopa effects on food intake but also that CRF neurons lie downstream of NPY neurons in the hierarchical forebrain system, thus controlling energy balance. Unexpectedly, dietary administration of haloperidol, a D2-receptor antagonist, cannot block dopamine effects but also induces a decline of the food intake. This decrease seems to be a side effect of haloperidol treatment since fish exhibited a decreased locomotor activity. We conclude that oral l-dopa inhibits sea bass food intake and growth. Mechanism could also involve an increase of hypothalamic serotoninergic tone. 相似文献
100.
Kavestri Yegambaram Esther M.M. Bulloch Richard L. Kingston 《Protein science : a publication of the Protein Society》2013,22(11):1502-1518
Abstract: Proteins are often classified in a binary fashion as either structured or disordered. However this approach has several deficits. Firstly, protein folding is always conditional on the physiochemical environment. A protein which is structured in some circumstances will be disordered in others. Secondly, it hides a fundamental asymmetry in behavior. While all structured proteins can be unfolded through a change in environment, not all disordered proteins have the capacity for folding. Failure to accommodate these complexities confuses the definition of both protein structural domains and intrinsically disordered regions. We illustrate these points with an experimental study of a family of small binding domains, drawn from the RNA polymerase of mumps virus and its closest relatives. Assessed at face value the domains fall on a structural continuum, with folded, partially folded, and near unstructured members. Yet the disorder present in the family is conditional, and these closely related polypeptides can access the same folded state under appropriate conditions. Any heuristic definition of the protein domain emphasizing conformational stability divides this domain family in two, in a way that makes no biological sense. Structural domains would be better defined by their ability to adopt a specific tertiary structure: a structure that may or may not be realized, dependent on the circumstances. This explicitly allows for the conditional nature of protein folding, and more clearly demarcates structural domains from intrinsically disordered regions that may function without folding. 相似文献