全文获取类型
收费全文 | 3905篇 |
免费 | 282篇 |
国内免费 | 4篇 |
专业分类
4191篇 |
出版年
2021年 | 49篇 |
2020年 | 41篇 |
2019年 | 32篇 |
2018年 | 54篇 |
2017年 | 33篇 |
2016年 | 67篇 |
2015年 | 94篇 |
2014年 | 152篇 |
2013年 | 165篇 |
2012年 | 217篇 |
2011年 | 208篇 |
2010年 | 135篇 |
2009年 | 148篇 |
2008年 | 204篇 |
2007年 | 188篇 |
2006年 | 179篇 |
2005年 | 186篇 |
2004年 | 159篇 |
2003年 | 142篇 |
2002年 | 130篇 |
2001年 | 55篇 |
2000年 | 73篇 |
1999年 | 69篇 |
1998年 | 55篇 |
1997年 | 39篇 |
1996年 | 45篇 |
1995年 | 35篇 |
1994年 | 35篇 |
1993年 | 44篇 |
1992年 | 65篇 |
1991年 | 65篇 |
1990年 | 54篇 |
1989年 | 50篇 |
1988年 | 54篇 |
1987年 | 42篇 |
1986年 | 38篇 |
1985年 | 45篇 |
1984年 | 55篇 |
1982年 | 34篇 |
1981年 | 35篇 |
1980年 | 37篇 |
1979年 | 31篇 |
1978年 | 37篇 |
1977年 | 42篇 |
1976年 | 31篇 |
1975年 | 36篇 |
1974年 | 37篇 |
1973年 | 30篇 |
1972年 | 28篇 |
1971年 | 27篇 |
排序方式: 共有4191条查询结果,搜索用时 21 毫秒
91.
Erik Ziegler Ariane Foret Laura Mascetti Vincenzo Muto Anahita Le Bourdiec-Shaffii Johan Stender Evelyne Balteau Vinciane Dideberg Vincent Bours Pierre Maquet Christophe Phillips 《PloS one》2013,8(7)
Brain-derived neurotrophic factor (BDNF) modulates the pruning of synaptically silent axonal arbors. The Met allele of the BDNF gene is associated with a reduction in the neurotrophin''s activity-dependent release. We used diffusion-weighted imaging to construct structural brain networks for 36 healthy subjects with known BDNF genotypes. Through permutation testing we discovered clear differences in connection strength between subjects carrying the Met allele and those homozygotic for the Val allele. We trained a Gaussian process classifier capable of identifying the subjects'' allelic group with 86% accuracy and high predictive value. In Met carriers structural connectivity was greatly increased throughout the forebrain, particularly in connections corresponding to the anterior and superior corona radiata as well as corticothalamic and corticospinal projections from the sensorimotor, premotor, and prefrontal portions of the internal capsule. Interhemispheric connectivity was also increased via the corpus callosum and anterior commissure, and extremely high connectivity values were found between inferior medial frontal polar regions via the anterior forceps. We propose that the decreased availability of BDNF leads to deficits in axonal maintenance in carriers of the Met allele, and that this produces mesoscale changes in white matter architecture. 相似文献
92.
S. Lai L. G. Gillis C. Mueller T. J. Bouma J. R. Guest K. S. Last A. D. Ziegler P. A. Todd 《Coral reefs (Online)》2013,32(4):1061-1064
We present the first experimental evidence of a coral (Oulastrea crispata) ingesting and assimilating seagrass material. Tropical seagrass meadows export a substantial portion of their productivity and can provide an important source of nutrients to neighbouring systems such as coral reefs; however, little is known about the mechanisms of this link. To investigate whether seagrass nutrient uptake via coral heterotrophy is possible, we conducted a feeding experiment with seagrass particulate and dissolved organic matter. Using gut extractions and stable isotope analyses, we determined that O. crispata ingested 15N-enriched seagrass particles and assimilated the nitrogen into its tissue at a rate of 0.75 μg N cm?2 h?1. Corals took up nitrogen from dissolved matter at a comparable rate of 0.98 μg N cm?2 h?1. While other ecological connections between seagrass meadows and reef ecosystems are well known, our results suggest a previously unstudied direct nutritional link between seagrasses and corals. 相似文献
93.
Hadhemi Kaddour Yosra Hamdi David Vaudry Magalie Basille Laurence Desrues Jérôme Leprince Hélène Castel Hubert Vaudry Marie‐Christine Tonon Mohamed Amri Olfa Masmoudi‐Kouki 《Journal of neurochemistry》2013,125(4):620-633
Oxidative stress, induced by various neurodegenerative diseases, initiates a cascade of events leading to apoptosis, and thus plays a critical role in neuronal injury. In this study, we have investigated the potential neuroprotective effect of the octadecaneuropeptide (ODN) on 6‐hydroxydopamine (6‐OHDA)‐induced oxidative stress and apoptosis in cerebellar granule neurons (CGN). ODN, which is produced by astrocytes, is an endogenous ligand for both central‐type benzodiazepine receptors (CBR) and a metabotropic receptor. Incubation of neurons with subnanomolar concentrations of ODN (10?18 to 10?12 M) inhibited 6‐OHDA‐evoked cell death in a concentration‐dependent manner. The effect of ODN on neuronal survival was abrogated by the metabotropic receptor antagonist, cyclo1–8[DLeu5]OP, but not by a CBR antagonist. ODN stimulated polyphosphoinositide turnover and ERK phosphorylation in CGN. The protective effect of ODN against 6‐OHDA toxicity involved the phospholipase C/ERK MAPK transduction cascade. 6‐OHDA treatment induced an accumulation of reactive oxygen species, an increase of the expression of the pro‐apoptotic gene Bax, a drop of the mitochondrial membrane potential and a stimulation of caspase‐3 activity. Exposure of 6‐OHDA‐treated cells to ODN blocked all the deleterious effects of the toxin. Taken together, these data demonstrate for the first time that ODN is a neuroprotective agent that prevents 6‐OHDA‐induced oxidative stress and apoptotic cell death. 相似文献
94.
Wendy E. Kaman Ingrid Voskamp-Visser Denise M.C. de Jongh Hubert P. Endtz Alex van Belkum John P. Hays Floris J. Bikker 《Analytical biochemistry》2013
Bacterial proteases play an important role in a broad spectrum of processes, including colonization, proliferation, and virulence. In this respect, bacterial proteases are potential biomarkers for bacterial diagnosis and targets for novel therapeutic protease inhibitors. To investigate these potential functions, the authors designed and used a protease substrate fluorescence resonance energy transfer (FRET) library comprising 115 short d- and l-amino-acid-containing fluorogenic substrates as a tool to generate proteolytic profiles for a wide range of bacteria. Bacterial specificity of the d-amino acid substrates was confirmed using enzymes isolated from both eukaryotic and prokaryotic organisms. Interestingly, bacterial proteases that are known to be involved in housekeeping and nutrition, but not in virulence, were able to degrade substrates in which a d-amino acid was present. Using our FRET peptide library and culture supernatants from a total of 60 different bacterial species revealed novel, bacteria-specific, proteolytic profiles, although in-species variation was observed for Pseudomonas aeruginosa, Porphyromonas gingivalis, and Staphylococcus aureus. Overall, the specific characteristic of our substrate peptide library makes it a rapid tool to high-throughput screen for novel substrates to detect bacterial proteolytic activity. 相似文献
95.
Sterols are required for cell‐fate commitment and maintenance of the stomatal lineage in Arabidopsis
Pingping Qian Bing Han Edith Forestier Zhihong Hu Na Gao Wenwen Lu Hubert Schaller Jia Li Suiwen Hou 《The Plant journal : for cell and molecular biology》2013,74(6):1029-1044
Asymmetric cell division is important for regulating cell proliferation and fate determination during stomatal development in plants. Although genes that control asymmetric division and cell differentiation in stomatal development have been reported, regulators controlling the process from asymmetric division to cell differentiation remain poorly understood. Here, we report a weak allele (fk–J3158) of the Arabidopsis sterol C–14 reductase gene FACKEL (FK) that shows clusters of small cells and stomata in leaf epidermis, a common phenomenon that is often seen in mutants defective in stomatal asymmetric division. Interestingly, the physical asymmetry of these divisions appeared to be intact in fk mutants, but the cell‐fate asymmetry was greatly disturbed, suggesting that the FK pathway links these two crucial events in the process of asymmetric division. Sterol profile analysis revealed that the fk–J3158 mutation blocked downstream sterol production. Further investigation indicated that cyclopropylsterol isomerase1 (cpi1), sterol 14α–demethylase (cyp51A2) and hydra1 (hyd1) mutants, corresponding to enzymes in the same branch of the sterol biosynthetic pathway, displayed defective stomatal development phenotypes, similar to those observed for fk. Fenpropimorph, an inhibitor of the FK sterol C–14 reductase in Arabidopsis, also caused these abnormal small‐cell and stomata phenotypes in wild‐type leaves. Genetic experiments demonstrated that sterol biosynthesis is required for correct stomatal patterning, probably through an additional signaling pathway that has yet to be defined. Detailed analyses of time‐lapse cell division patterns, stomatal precursor cell division markers and DNA ploidy suggest that sterols are required to properly restrict cell proliferation, asymmetric fate specification, cell‐fate commitment and maintenance in the stomatal lineage cells. These events occur after physical asymmetric division of stomatal precursor cells. 相似文献
96.
97.
J. Michael Conlon Manju Prajeep Milena Mechkarska Laurent Coquet Jérôme Leprince Thierry Jouenne Hubert Vaudry Jay D. King 《Comparative biochemistry and physiology. Part D, Genomics & proteomics》2013,8(4):352-357
The family Pipidae comprises the genera Hymenochirus, Pipa, Pseudhymenochirus, Silurana, and Xenopus but phylogenetic relationships within the family are unclear. Peptidomic analysis of norepinephrine-stimulated skin secretions from Pseudhymenochirus merlini Chabanaud, 1920, the single species within the genus Pseudhymenochirus, led to identification of 13 host-defense peptides with antimicrobial activity. Two peptides (hymenochirin-1Pa and -1Pb) show structural similarity to hymenochirin-1B from Hymenochirus boettgeri and eight peptides (hymenochirin-5Pa, -5Pb, -5Pc, -5Pd, -5Pe, -5Pf, 5Pg and -5Ph) are structurally similar to each other and to hymenochirin-5B from H. boettgeri. Two peptides differing by a single amino acid (IKIPSFFRNILKKVGKEAVSLM/I AGALKQS), termed pseudhymenochirin-1Pa and -1Pb, and pseudhymenochirin-2Pa (GIFPIFAKLLGKVIKVASSLISKGRTE) do not resemble host-defense peptides previously isolated from pipid frogs. Hymenochirin-5Pe was the most abundant peptide in the secretions and hymenochirin-1Pa the most potent against Staphylococcus aureus (MIC = 2.5 μM) and Escherichia coli (MIC = 10 μM). The data support a close phylogenetic relationship between Hymenochirus and Pseudhymenochirus that is distinct from the Xenopodinae (Xenopus + Silurana) clade with Pipa sister-group to all other extant pipids. 相似文献
98.
99.
Mariola M. Marcinkiewicz Sandy T. Baker Jichuan Wu Terrence L. Hubert Marla R. Wolfson 《PloS one》2016,11(3)
The in vivo ovine model provides a clinically relevant platform to study cardiopulmonary mechanisms and treatments of disease; however, a robust ovine primary alveolar epithelial type II (ATII) cell culture model is lacking. The objective of this study was to develop and optimize ovine lung tissue cryopreservation and primary ATII cell culture methodologies for the purposes of dissecting mechanisms at the cellular level to elucidate responses observed in vivo. To address this, we established in vitro submerged and air-liquid interface cultures of primary ovine ATII cells isolated from fresh or cryopreserved lung tissues obtained from mechanically ventilated sheep (128 days gestation—6 months of age). Presence, abundance, and mRNA expression of surfactant proteins was assessed by immunocytochemistry, Western Blot, and quantitative PCR respectively on the day of isolation, and throughout the 7 day cell culture study period. All biomarkers were significantly greater from cells isolated from fresh than cryopreserved tissue, and those cultured in air-liquid interface as compared to submerged culture conditions at all time points. Surfactant protein expression remained in the air-liquid interface culture system while that of cells cultured in the submerged system dissipated over time. Despite differences in biomarker magnitude between cells isolated from fresh and cryopreserved tissue, cells isolated from cryopreserved tissue remained metabolically active and demonstrated a similar response as cells from fresh tissue through 72 hr period of hyperoxia. These data demonstrate a cell culture methodology using fresh or cryopreserved tissue to support study of ovine primary ATII cell function and responses, to support expanded use of biobanked tissues, and to further understanding of mechanisms that contribute to in vivo function of the lung. 相似文献
100.
Kyrill S. Rogacev Gunnar H. Heine Günther Silbernagel Marcus E. Kleber Sarah Seiler Insa Emrich Simone Lennartz Christian Werner Adam M. Zawada Danilo Fliser Michael B?hm Winfried M?rz Hubert Scharnagl Ulrich Laufs 《PloS one》2016,11(1)