全文获取类型
收费全文 | 15110篇 |
免费 | 961篇 |
国内免费 | 3篇 |
出版年
2023年 | 89篇 |
2022年 | 169篇 |
2021年 | 390篇 |
2020年 | 304篇 |
2019年 | 315篇 |
2018年 | 385篇 |
2017年 | 353篇 |
2016年 | 533篇 |
2015年 | 813篇 |
2014年 | 873篇 |
2013年 | 1023篇 |
2012年 | 1303篇 |
2011年 | 1156篇 |
2010年 | 747篇 |
2009年 | 703篇 |
2008年 | 937篇 |
2007年 | 878篇 |
2006年 | 804篇 |
2005年 | 764篇 |
2004年 | 715篇 |
2003年 | 637篇 |
2002年 | 599篇 |
2001年 | 133篇 |
2000年 | 89篇 |
1999年 | 124篇 |
1998年 | 131篇 |
1997年 | 119篇 |
1996年 | 99篇 |
1995年 | 89篇 |
1994年 | 88篇 |
1993年 | 58篇 |
1992年 | 53篇 |
1991年 | 61篇 |
1990年 | 57篇 |
1989年 | 31篇 |
1988年 | 36篇 |
1987年 | 26篇 |
1986年 | 20篇 |
1985年 | 39篇 |
1984年 | 54篇 |
1983年 | 20篇 |
1982年 | 25篇 |
1981年 | 26篇 |
1980年 | 27篇 |
1979年 | 16篇 |
1978年 | 19篇 |
1977年 | 21篇 |
1976年 | 17篇 |
1975年 | 18篇 |
1969年 | 10篇 |
排序方式: 共有10000条查询结果,搜索用时 78 毫秒
931.
Diet and exercise improve chemoreflex sensitivity in patients with metabolic syndrome and obstructive sleep apnea 下载免费PDF全文
Cristiane Maki‐Nunes Edgar Toschi‐Dias Felipe X. Cepeda Maria Urbana P.B. Rondon Maria‐Janieire N. N. Alves Raffael F. Fraga Ana Maria F. W. Braga Adriana M. Aguilar Aline C. Amaro Luciano F. Drager Geraldo Lorenzi‐Filho Carlos E. Negrão Ivani C. Trombetta 《Obesity (Silver Spring, Md.)》2015,23(8):1582-1590
932.
933.
934.
Laura D. Bertola Laura Tensen Pim van Hooft Paula A. White Carlos A. Driscoll Philipp Henschel Anthony Caragiulo Isabela Dias-Freedman Etotépé A. Sogbohossou Pricelia N. Tumenta Tuqa H. Jirmo Geert R. de Snoo Hans H. de Iongh Klaas Vrieling 《PloS one》2015,10(10)
The evolutionary history of a species is key for understanding the taxonomy and for the design of effective management strategies for species conservation. The knowledge about the phylogenetic position of the lion (Panthera leo) in West/Central Africa is largely based on mitochondrial markers. Previous studies using mtDNA only have shown this region to hold a distinct evolutionary lineage. In addition, anthropogenic factors have led to a strong decline in West/Central African lion numbers, thus, the conservation value of these populations is particularly high. Here, we investigate whether autosomal markers are concordant with previously described phylogeographic patterns, and confirm the unique position of the West/Central African lion. Analysis of 20 microsatellites and 1,454 bp of the mitochondrial DNA in 16 lion populations representing the entire geographic range of the species found congruence in both types of markers, identifying four clusters: 1) West/Central Africa, 2) East Africa, 3) Southern Africa and 4) India. This is not in line with the current taxonomy, as defined by the IUCN, which only recognizes an African and an Asiatic subspecies. There are no indications that genetic diversity in West/Central Africa lions is lower than in either East or Southern Africa, however, given this genetic distinction and the recent declines of lion numbers in this region, we strongly recommend prioritization of conservation projects in West/Central Africa. As the current taxonomic nomenclature does not reflect the evolutionary history of the lion, we suggest that a taxonomic revision of the lion is warranted. 相似文献
935.
Eloy Martínez-Heras Federico Varriano Vesna Pr?kovska Carlos Laredo Magí Andorrà Elena H. Martínez-Lapiscina Anna Calvo Erika Lampert Pablo Villoslada Albert Saiz Alberto Prats-Galino Sara Llufriu 《PloS one》2015,10(9)
The optic radiation (OR) is one of the major components of the visual system and a key structure at risk in white matter diseases such as multiple sclerosis (MS). However, it is challenging to perform track reconstruction of the OR using diffusion MRI due to a sharp change of direction in the Meyer’s loop and the presence of kissing and crossing fibers along the pathway. As such, we aimed to provide a highly precise and reproducible framework for tracking the OR from thalamic and visual cortex masks. The framework combined the generation of probabilistic streamlines by high order fiber orientation distributions estimated with constrained spherical deconvolution and an automatic post-processing based on anatomical exclusion criteria (AEC) to compensate for the presence of anatomically implausible streamlines. Specifically, those ending in the contralateral hemisphere, cerebrospinal fluid or grey matter outside the visual cortex were automatically excluded. We applied the framework to two distinct high angular resolution diffusion-weighted imaging (HARDI) acquisition protocols on one cohort, comprised of ten healthy volunteers and five MS patients. The OR was successfully delineated in both HARDI acquisitions in the healthy volunteers and MS patients. Quantitative evaluation of the OR position was done by comparing the results with histological reference data. Compared with histological mask, the OR reconstruction into a template (OR-TCT) was highly precise (percentage of voxels within the OR-TCT correctly defined as OR), ranging from 0.71 to 0.83. The sensitivity (percentage of voxels in histological reference mask correctly defined as OR in OR-TCT) ranged from 0.65 to 0.81 and the accuracy (measured by F1 score) was 0.73 to 0.77 in healthy volunteers. When AEC was not applied the precision and accuracy decreased. The absolute agreement between both HARDI datasets measured by the intraclass correlation coefficient was 0.73. This improved framework allowed us to reconstruct the OR with high reliability and accuracy independently of the acquisition parameters. Moreover, the reconstruction was possible even in the presence of tissue damage due to MS. This framework could also be applied to other tracts with complex configuration. 相似文献
936.
Cre recombinase activity is inhibited in vivo but not ex vivo by a mutation in the asymmetric spacer region of the distal loxP site 下载免费PDF全文
The cre/loxP recombination system is a valuable tool used to generate tissue specific genomic rearrangements in mouse models. The deletion of a region of interest flanked by two loxP sites is accomplished by the recombinase (cre) enzyme, which binds to the inverted repeat segments of two loxP sites and recognition of a conserved TA sequence in the asymmetric central spacer region “ATAACTTCGTATA ‐NNNTANNN‐TATACGAAGTTAT. In vivo, we found that a single T to C mutation at position 4 of the central spacer region in the distal (3′) loxP site, completely inhibited the recombination reaction in two conditional mouse models. These mice were generated using a mitochondrial methionyl‐tRNA formyltransferase (Mtfmt) gene targeted construct and cre transgene under the control of tissue‐specific promoters: calcium/calmodulin‐dependent kinase II alpha (Camk2a‐cre) and myosin light polypeptide 1 (Myl1‐cre). Surprisingly, transient transfection of a plasmid expressing cre in dermal fibroblasts derived from the same mutant floxed Mtfmt(loxP/loxP) mice line, successfully deleted the region of interest. This study demonstrates the sequence specificity required in vivo, the possibility of bypassing this limitation by expressing high levels of cre recombinase ex vivo and raises concerns related to the quality control of large scale production of gene targeted constructs and mice. genesis 53:695–700, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
937.
Mirele da Silveira Vasconcelos Neuza F Gomes-Rochette Maria Liduína M de Oliveira Diana Célia S Nunes-Pinheiro Adriana R Tomé Francisco Yuri Maia de Sousa Francisco Geraldo M Pinheiro Carlos Farley H Moura Maria Raquel A Miranda Erika Freitas Mota Dirce Fernandes de Melo 《Experimental biology and medicine (Maywood, N.J.)》2015,240(12):1648-1655
Cashew apple is a tropical pseudofruit consumed as juice due to its excellent nutritional and sensory properties. In spite of being well known for its important antioxidant properties, the cashew apple has not been thoroughly investigated for its therapeutic potential. Thereby, this study evaluated the antioxidant capacity, anti-inflammatory, and wound-healing activities of cashew apple juice. Juices from ripe and immature cashew apples were analyzed for antioxidant, anti-inflammatory, and wound-healing properties. Those were evaluated in murine models of xylene-induced ear edema and wound excision. Swiss mice were treated with cashew juice by gavage. Edema thickness was measured and skin lesions were analyzed by planimetry and histology. Both antioxidant content and total antioxidant activity were higher in ripe cashew apple juice (RCAJ) than in unripe cashew apple juice (UNCAJ). The UNCAJ presented the main anti-inflammatory activity by a significant inhibition of ear edema (66.5%) when compared to RCAJ (10%). Moreover, UNCAJ also showed the best result for wound contraction (86.31%) compared to RCAJ (67.54%). Despite of higher antioxidant capacity, RCAJ did not promote better anti-inflammatory, and healing responses, which may be explained by the fact that treatment increased antioxidants level leading to a redox “imbalance” turning down the inflammatory response modulation exerted by reactive oxygen species (ROS). The results suggest that UNCAJ presents a greater therapeutic activity due to a synergistic effect of its phytochemical components, which improve the immunological mechanisms as well as an optimal balance between ROS and antioxidants leading to a better wound healing process. 相似文献
938.
Rebecca A. Drummond Amanda L. Collar Muthulekha Swamydas Carlos A. Rodriguez Jean K. Lim Laura M. Mendez Danielle L. Fink Amy P. Hsu Bing Zhai Hatice Karauzum Constantinos M. Mikelis Stacey R. Rose Elise M. N. Ferre Lynne Yockey Kimberly Lemberg Hye Sun Kuehn Sergio D. Rosenzweig Xin Lin Prashant Chittiboina Sandip K. Datta Thomas H. Belhorn Eric T. Weimer Michelle L. Hernandez Tobias M. Hohl Douglas B. Kuhns Michail S. Lionakis 《PLoS pathogens》2015,11(12)
Candida is the most common human fungal pathogen and causes systemic infections that require neutrophils for effective host defense. Humans deficient in the C-type lectin pathway adaptor protein CARD9 develop spontaneous fungal disease that targets the central nervous system (CNS). However, how CARD9 promotes protective antifungal immunity in the CNS remains unclear. Here, we show that a patient with CARD9 deficiency had impaired neutrophil accumulation and induction of neutrophil-recruiting CXC chemokines in the cerebrospinal fluid despite uncontrolled CNS Candida infection. We phenocopied the human susceptibility in Card9
-/- mice, which develop uncontrolled brain candidiasis with diminished neutrophil accumulation. The induction of neutrophil-recruiting CXC chemokines is significantly impaired in infected Card9
-/- brains, from both myeloid and resident glial cellular sources, whereas cell-intrinsic neutrophil chemotaxis is Card9-independent. Taken together, our data highlight the critical role of CARD9-dependent neutrophil trafficking into the CNS and provide novel insight into the CNS fungal susceptibility of CARD9-deficient humans. 相似文献
939.
Ata Ghavidel Kunal Baxi Vladimir Ignatchenko Martin Prusinkiewicz Terra G. Arnason Thomas Kislinger Carlos E. Carvalho Troy A. A. Harkness 《PLoS genetics》2015,11(8)
Proliferating eukaryotic cells undergo a finite number of cell divisions before irreversibly exiting mitosis. Yet pathways that normally limit the number of cell divisions remain poorly characterized. Here we describe a screen of a collection of 3762 single gene mutants in the yeast Saccharomyces cerevisiae, accounting for 2/3 of annotated yeast ORFs, to search for mutants that undergo an atypically high number of cell divisions. Many of the potential longevity genes map to cellular processes not previously implicated in mitotic senescence, suggesting that regulatory mechanisms governing mitotic exit may be broader than currently anticipated. We focused on an ER-Golgi gene cluster isolated in this screen to determine how these ubiquitous organelles integrate into mitotic longevity. We report that a chronic increase in ER protein load signals an expansion in the assembly of autophagosomes in an Ire1-independent manner, accelerates trafficking of high molecular weight protein aggregates from the cytoplasm to the vacuoles, and leads to a profound enhancement of daughter cell production. We demonstrate that this catabolic network is evolutionarily conserved, as it also extends reproductive lifespan in the nematode Caenorhabditis elegans. Our data provide evidence that catabolism of protein aggregates, a natural byproduct of high protein synthesis and turn over in dividing cells, is among the drivers of mitotic longevity in eukaryotes. 相似文献
940.
Ayelen M Distéfano Matías A Vali?as Denise Scuffi Lorenzo Lamattina Arjen ten Have Carlos García-Mata Ana M Laxalt 《Plant signaling & behavior》2015,10(11)
Phospholipase D (PLD) is involved in different plant processes, ranging from responses to abiotic and biotic stress to plant development. Phospholipase Dδ (PLDδ) is activated in dehydration and salt stress, producing the lipid second messenger phosphatidic acid. In this work we show that pldδ Arabidopsis mutants were more tolerant to severe drought than wild-type plants. PLDδ has been shown to be required for ABA regulation of stomatal closure of isolated epidermal peels. However, there was no significant difference in stomatal conductance at the whole plant level between wild-type and pldδ mutants. Since PLD hydrolyses structural phospholipids, then we looked at membrane integrity. Ion leakage measurements showed that during dehydration of leaf discs pldδ mutant has less membrane degradation compared to the wild-type. We further analyzed the mutants and showed that pldδ have higher mRNA levels of RAB18 and RD29A compared to wild-type plants under normal growth conditions. Transient expression of AtPLDδ in Nicotiana benthamiana plants induced a wilting phenotype. These findings suggest that, in wt plants PLDδ disrupt membranes in severe drought stress and, in the absence of the protein (PLDδ knock-out) might drought-prime the plants, making them more tolerant to severe drought stress. The results are discussed in relation to PLDδ role in guard cell signaling and drought tolerance. 相似文献