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41.
Yu-Tao Xiang Robert W. Buchanan Gabor S. Ungvari Helen F. K. Chiu Kelly Y. C. Lai You-Hong Li Tian-Mei Si Chuan-Yue Wang Edwin H. M. Lee Yan-Ling He Shu-Yu Yang Mian-Yoon Chong Ee-Heok Kua Senta Fujii Kang Sim Michael K. H. Yong Jitendra K. Trivedi Eun-Kee Chung Pichet Udomratn Kok-Yoon Chee Norman Sartorius Chay-Hoon Tan Naotaka Shinfuku 《PloS one》2013,8(6)
42.
43.
Andreas Schmid Zoltan Sutto Nathalie Schmid Lisa Novak Pedro Ivonnet Gabor Horvath Gregory Conner Nevis Fregien Matthias Salathe 《The Journal of biological chemistry》2010,285(39):29998-30007
Human airway cilia contain soluble adenylyl cyclase (sAC) that produces cAMP upon HCO3−/CO2 stimulation to increase ciliary beat frequency (CBF). Because apical HCO3− exchange depends on cystic fibrosis transmembrane conductance regulator (CFTR), malfunctioning CFTR might impair sAC-mediated CBF regulation in cells from patients with cystic fibrosis (CF). By Western blot, sAC isoforms are equally expressed in normal and CF airway epithelial cells, but CBF decreased more in CF than normal cells upon increased apical HCO3−/CO2 exposure in part because of greater intracellular acidification from unbalanced CO2 influx (estimated by 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) fluorescence). Importantly, ciliated cell-specific cAMP production (estimated by FRET fluorescence ratio changes of tagged cAMP-dependent protein kinase (PKA) subunits expressed under a ciliated cell-specific promoter) in response to increased apical HCO3−/CO2 perfusion was higher in normal compared with CF cells. Inhibition of bicarbonate influx via CFTR (CFTRinh172) and inhibition of sAC (KH7) and PKA activation (H89) led to larger CBF declines in normal cells, now comparable with changes seen in CF cells. These inhibitors also reduced FRET changes in normal cells to the level of CF cells with the expected exception of H89, which does not prevent dissociation of the fluorescently tagged PKA subunits. Basolateral permeabilization and subsequent perfusion with HCO3−/CO2 rescued CBF and FRET changes in CF cells to the level of normal cells. These results suggest that CBF regulation by sAC-produced cAMP could be impaired in CF, thereby possibly contributing to mucociliary dysfunction in this disease, at least during disease exacerbations when airway acidification is common. 相似文献
44.
Deanna M Church Valerie A Schneider Karyn Meltz Steinberg Michael C Schatz Aaron R Quinlan Chen-Shan Chin Paul A Kitts Bronwen Aken Gabor T Marth Michael M Hoffman Javier Herrero M Lisandra Zepeda Mendoza Richard Durbin Paul Flicek 《Genome biology》2015,16(1)
The human genome reference assembly is crucial for aligning and analyzing sequence data, and for genome annotation, among other roles. However, the models and analysis assumptions that underlie the current assembly need revising to fully represent human sequence diversity. Improved analysis tools and updated data reporting formats are also required. 相似文献
45.
Role of astrocytes in neurovascular coupling 总被引:1,自引:0,他引:1
Neural activity is intimately tied to blood flow in the brain. This coupling is specific enough in space and time that modern imaging methods use local hemodynamics as a measure of brain activity. In this review, we discuss recent evidence indicating that neuronal activity is coupled to local blood flow changes through an intermediary, the astrocyte. We highlight unresolved issues regarding the role of astrocytes and propose ways to address them using novel techniques. Our focus is on cellular level analysis in?vivo, but we also relate mechanistic insights gained from ex?vivo experiments to native tissue. We also review some strategies to harness advances in optical and genetic methods to study neurovascular coupling in the intact brain. 相似文献
46.
Makarava N Kovacs GG Savtchenko R Alexeeva I Budka H Rohwer RG Baskakov IV 《PLoS pathogens》2011,7(12):e1002419
The transmissible agent of prion disease consists of a prion protein in its abnormal, β-sheet rich state (PrP(Sc)), which is capable of replicating itself according to the template-assisted mechanism. This mechanism postulates that the folding pattern of a newly recruited polypeptide chain accurately reproduces that of a PrP(Sc) template. Here we report that authentic PrP(Sc) and transmissible prion disease can be generated de novo in wild type animals by recombinant PrP (rPrP) amyloid fibrils, which are structurally different from PrP(Sc) and lack any detectable PrP(Sc) particles. When induced by rPrP fibrils, a long silent stage that involved two serial passages preceded development of the clinical disease. Once emerged, the prion disease was characterized by unique clinical, neuropathological, and biochemical features. The long silent stage to the disease was accompanied by significant transformation in neuropathological properties and biochemical features of the proteinase K-resistant PrP material (PrPres) before authentic PrP(Sc) evolved. The current work illustrates that transmissible prion diseases can be induced by PrP structures different from that of authentic PrP(Sc) and suggests that a new mechanism different from the classical templating exists. This new mechanism designated as "deformed templating" postulates that a change in the PrP folding pattern from the one present in rPrP fibrils to an alternative specific for PrP(Sc) can occur. The current work provides important new insight into the mechanisms underlying genesis of the transmissible protein states and has numerous implications for understanding the etiology of neurodegenerative diseases. 相似文献
47.
Swee Tin Aw Michael John Todd Nadine Lehnen Grace Elizabeth Aw Konrad Peter Weber Thomas Eggert Gabor Michael Halmagyi 《PloS one》2013,8(12)
Background
Vestibular reflexes, evoked by human electrical (galvanic) vestibular stimulation (EVS), are utilized to assess vestibular function and investigate its pathways. Our study aimed to investigate the electrically-evoked vestibulo-ocular reflex (eVOR) output after bilateral and unilateral vestibular deafferentations to determine the characteristics for interpreting unilateral lesions such as vestibular schwannomas.Methods
EVOR was recorded with dual-search coils as binocular three-dimensional eye movements evoked by bipolar 100 ms-step at EVS intensities of [0.9, 2.5, 5.0, 7.5, 10.0]mA and unipolar 100 ms-step at 5 mA EVS intensity. Five bilateral vestibular deafferented (BVD), 12 unilateral vestibular deafferented (UVD), four unilateral vestibular schwannoma (UVS) patients and 17 healthy subjects were tested with bipolar EVS, and five UVDs with unipolar EVS.Results
After BVD, bipolar EVS elicited no eVOR. After UVD, bipolar EVS of one functioning ear elicited bidirectional, excitatory eVOR to cathodal EVS with 9 ms latency and inhibitory eVOR to anodal EVS, opposite in direction, at half the amplitude with 12 ms latency, exhibiting an excitatory-inhibitory asymmetry. The eVOR patterns from UVS were consistent with responses from UVD confirming the vestibular loss on the lesion side. Unexpectedly, unipolar EVS of the UVD ear, instead of absent response, evoked one-third the bipolar eVOR while unipolar EVS of the functioning ear evoked half the bipolar response.Conclusions
The bidirectional eVOR evoked by bipolar EVS from UVD with an excitatory-inhibitory asymmetry and the 3 ms latency difference between normal and lesion side may be useful for detecting vestibular lesions such as UVS. We suggest that current spread could account for the small eVOR to 5 mA unipolar EVS of the UVD ear. 相似文献48.
An alpha/beta-fold C--C bond hydrolase is involved in a central step of nicotine catabolism by Arthrobacter nicotinovorans 下载免费PDF全文
The enzyme catalyzing the hydrolytic cleavage of 2,6-dihydroxypseudooxynicotine to 2,6-dihydroxypyridine and gamma-N-methylaminobutyrate was found to be encoded on pAO1 of Arthrobacter nicotinovorans. The new enzyme answers an old question about nicotine catabolism and may be the first C--C bond hydrolase that is involved in the biodegradation of a heterocyclic compound. 相似文献
49.
Presynaptic modulation by eicosanoids in cortical synaptosomes 总被引:1,自引:0,他引:1
In continuing experiments to determine the ionic basis of inhibitory presynaptic modulation, rat cortical synaptosomes were employed and receptor-activated K+ efflux was determined with a K+ sensitive electrode. When synaptosomes were sub-optimally depolarized by veratridine, the addition of agents that activated purinergic, 2, muscarinic and opioid receptors all promoted K+ efflux. With 2-chloroadenosine as a model inhibitory presynaptic modulator, the increased K+ efflux evoked by this agent was blocked by the cyclooxygenase inhibitor indomethacin suggesting that arachidonic acid or its metabolites was an intermediary in opening the channel. When arachidonic acid and PGE2 were tested, both promoted K+ efflux that was inhibited by dendrotoxin and mast cell degranulating peptide, two agents that are known to inhibit a delayed rectifier K+ current. Our results suggest that via eicosanoid second messengers, inhibitory presynaptic modulators open a sub-class of K channels that hyperpolarize nerve terminals, therefore less Ca2+ would enter per nerve impulse and thus the evoked release of neurotransmitters would be decreased.Abbreviations DTX
dendrotoxin
- MCDP
mast cell degranulating peptide
- NHGA
norhydroguairetic acid
- PGE2
prostaglandin E2 相似文献
50.