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51.
Edith Hamel Jessika Royea Brice Ongali Xin-Kang Tong 《Cellular and molecular neurobiology》2016,36(2):219-232
Alzheimer’s disease (AD) is a multifactorial and multifaceted disease for which we currently have very little to offer since there is no curative therapy, with only limited disease-modifying drugs. Recent studies in AD mouse models that recapitulate the amyloid-β (Aβ) pathology converge to demonstrate that it is possible to salvage cerebrovascular function with a variety of drugs and, particularly, therapies used to treat cardiovascular diseases such as hypercholesterolemia and hypertension. These drugs can reestablish dilatory function mediated by various endothelial and smooth muscle ion channels as well as nitric oxide availability, benefits that result in normalized brain perfusion. These cerebrovascular benefits would favor brain perfusion, which may help maintain neuronal function and, possibly, delay cognitive failure. However, restoring cerebrovascular function in AD mouse models was not necessarily accompanied by rescue of cognitive deficits related to spatial learning and memory. The results with cardiovascular therapies rather suggest that drugs originally designed to treat cardiovascular diseases that concurrently restore cerebrovascular and cognitive function do so through their pleiotropic effects. Specifically, recent findings suggest that these drugs act directly on brain cells and neuronal pathways involved in memory formation, hence, working simultaneously albeit independently on neuronal and vascular targets. These findings may help select medications for patients with cardiovascular diseases at risk of developing AD with increasing age. Further, they may identify molecular targets for recovering memory pathways that bear potential for new therapeutic avenues. 相似文献
52.
Bernhard Benkel Sonja Kollers Ruedi Fries Alexei Sazanov Erin Yoshida Edith Valle Jon Davoren Donal Hickey 《Mammalian genome》2005,16(3):194-200
AMP-activated protein kinase (AMPK) represents the mammalian form of the core component of a kinase cascade that is conserved between fungi, plants, and animals. AMPK plays a major role in protecting mammalian cells from metabolic stress by switching off biosynthetic pathways that require ATP and switching on ATP-regenerating pathways. In this report, we describe the isolation and characterization of the gene for the noncatalytic bovine gamma1 subunit of AMPK. The bovine ampkgamma1 (PRKAG1) gene spans in excess of 14 kb and is located at BTA 5q21-q22. It consists of 12 exons ranging in size from 38 b to 166 b, interspersed with 11 introns that range between 97 b and 6753 b in length. The coding region of the bovine gene shares 93% and 90% nucleotide sequence similarity with its human and rat counterparts, and the bovine AMPKgamma1 protein is 98% and 95% identical to its human and rat homologs, respectively, in amino acid sequence. SNP discovery using a cattle DNA panel revealed a number of polymorphisms that may be useful for the evaluation of ampkgamma1 as a candidate gene for energy metabolism-related production traits. 相似文献
53.
Astrocyte pVHL and HIF-α isoforms are required for embryonic-to-adult vascular transition in the eye
Kurihara T Westenskow PD Krohne TU Aguilar E Johnson RS Friedlander M 《The Journal of cell biology》2011,195(4):689-701
Successful transition from embryonic to adult circulation is critical for survival of mammalian organisms. This shift occurs in the central cardiovascular circulation and in the eye as oxygen tension increases. However, its regulation is not well understood. We have used combinatorial gene deletion and overexpression assays to assess the effect of astrocyte-targeted deletion of von Hippel-Lindau tumor suppressor (Vhl), hypoxia-inducible factor-αs (Hif-αs), and Vegf on the normal regression of the hyaloidal vessels, the fetal ocular circulation system. Astrocytic Vhl deletion induced accelerated hyaloidal regression and subsequent massive secondary outgrowth. Combinatorial gene deletion involving Vhl, Hif-αs, and Vegf genes revealed that HIF-2α/vascular endothelial growth factor signaling induces secondary outgrowth in Vhl mutants. Conversely, HIF-1α regulated macrophage migration inhibitory factor and promoted macrophage infiltration that accelerates hyaloidal vessel regression. The phenotype observed in Vhl mutants strongly resembles human persistent hyperplastic primary vitreous cases and may provide insights into vascular remodeling mechanisms in other systems. 相似文献
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Zusammenfassung
Anemone apennina gehört in die kleine Grappe der einkeimblättrigen Dikotylen-Arten.Der einzige Kotyledo wird lateral angelegt, drängt aber den Sproßvegetationspunkt später etwas zur Seite. Von der Anlage eines zweiten Kotyledos fehlt jede Spur.Weder der Embryogenese noch der Entwicklungsgeschichte und der Anatomie der Keimpflanzen sind Hinweise für das Vorliegen einer kongenitalen Verwachsung zweier Kotyledonen (Synkotylie) zu entnehmen.Der Kotyledo ist in gerader Linie über dem einen Pol der Xylemplatte der diarchen Keimachsenstele inseriert. Der Kotyledonarstiel wird von einem einfachen Leitstrang durchzogen, der im basalen Teil als diarche Stele und im apikalen als kollaterales Bündel ausgebildet ist. Die Nervatur der zweiteiligen Kotyledonarspreite macht wahrscheinlich, daß es sich um ein asymmetrisch fiederteiliges Blatt handelt.Daraus ergibt sich, daß bei A.apennina eine echte Einkeimblättrigkeit vorliegt, in dem Sinne, daß das einzige Keimblatt einem der beiden Keimblätter verwandter Arten homolog ist.Wir danken der Deutschen Forschungsgemeinschaft für die Unterstützung unserer Arbeiten. 相似文献
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Phenylalanine tolerance tests were performed on four untreated children with phenylketonuria, aged 8 to 12 years, before and after 14 days of folic acid administration (70 mg./day). No significant changes were noted in the phenylalanine tolerance tests or in the general condition of the patients. This study was carried out because of recent findings that a folic acid derivative is a co-factor in the conversion of phenylalanine to tyrosine. 相似文献
58.
Total aluminum, chromium, copper, iron, manganese, and nickel were determined in black tea, green tea, Hibiscus sabdariffa, and Ilex paraguariensis (mate) by electrothermal atomic absorption spectrometry after nitric/perchloric acid digestion. In each case, one ground
sample of commercially available leafy material was prepared and three 0.5-g subsamples were run in parallel. The infusions
were also analyzed and the percentage of each element leached into the liquor was evaluated. The obtained results indicated
that hibiscus and mate contained lower levels of aluminum (272±19 μg/g and 369±22 μg/g, respectively) as referred to black
tea (759±31 μg/g) or green tea (919±29 μg/g) and suggested that mate drinking could be a good dietary source of essential
micronutrient manganese (total content 2223±110 μg/g, 48.1% leached to the infusion). It was also found that the infusion
of hibiscus could supply greater amounts of iron (111±5 μg/g total, 40.5% leached) and copper (5.9±0.3 μg/g total, 93.4% leached)
as compared to other infusions. Moreover, it was found that the percentage of element leached to the infusion was strongly
related to the tannins content in the beverage (correlation coefficients >0.82 with the exception for nickel); for lower tannins
level, better leaching was observed. 相似文献
59.
David Wragg Elizabeth A. J. Cook Perle Latr de Lat Tatjana Sitt Johanneke D. Hemmink Maurine C. Chepkwony Regina Njeru E. Jane Poole Jessica Powell Edith A. Paxton Rebecca Callaby Andrea Talenti Antoinette A. Miyunga Gideon Ndambuki Stephen Mwaura Harriet Auty Oswald Matika Musa Hassan Karen Marshall Timothy Connelley Liam J. Morrison B. Mark deC. Bronsvoort W. Ivan Morrison Philip G. Toye James G. D. Prendergast 《PLoS genetics》2022,18(4)
East Coast fever, a tick-borne cattle disease caused by the Theileria parva parasite, is among the biggest natural killers of cattle in East Africa, leading to over 1 million deaths annually. Here we report on the genetic analysis of a cohort of Bos indicus (Boran) cattle demonstrating heritable tolerance to infection with T. parva (h2 = 0.65, s.e. 0.57). Through a linkage analysis we identify a 6 Mb genomic region on bovine chromosome 15 that is significantly associated with survival outcome following T. parva exposure. Testing this locus in an independent cohort of animals replicates this association with survival following T. parva infection. A stop gained variant in a paralogue of the FAF1 gene in this region was found to be highly associated with survival across both related and unrelated animals, with only one of the 20 homozygote carriers (T/T) of this change succumbing to the disease in contrast to 44 out of 97 animals homozygote for the reference allele (C/C). Consequently, we present a genetic locus linked to tolerance of one of Africa’s most important cattle diseases, raising the promise of marker-assisted selection for cattle that are less susceptible to infection by T. parva. 相似文献
60.
Pitre Nandan N. Moses J. B. Tzeng Edith Abramowitch Steven Velankar Sachin S. 《Biomechanics and modeling in mechanobiology》2023,22(3):1083-1094
Biomechanics and Modeling in Mechanobiology - Composites comprising crimped fibers of finite length embedded in a soft matrix have the potential to mimic the strain-hardening behavior of tissues... 相似文献