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991.
992.
Pathological conditions affect several stages of neurogenesis in the adult brain, including proliferation, survival, cell fate, migration, and functional integration. Here we explored how a pathological environment modulates the heterogeneous afferent synaptic input that shapes the functional properties of newly formed neurons. We analyzed the expression of adhesion molecules and other synaptic proteins on adult-born hippocampal neurons formed after electrically-induced partial status epilepticus (pSE). New cells were labeled with a GFP-retroviral vector one week after pSE. One and three weeks thereafter, synaptic proteins were present on dendritic spines and shafts, but without differences between pSE and control group. In contrast, at six weeks, we found fewer dendritic spines and decreased expression of the scaffolding protein PSD-95 on spines, without changes in expression of the adhesion molecules N-cadherin or neuroligin-1, primarily located at excitatory synapses. Moreover, we detected an increased expression of the inhibitory scaffolding protein gephyrin in newborn but not mature neurons after SE. However, this increase was not accompanied by a difference in GABA expression, and there was even a region-specific decrease in the adhesion molecule neuroligin-2 expression, both in newborn and mature neurons. Neuroligin-2 clusters co-localized with presynaptic cholecystokinin terminals, which were also reduced. The expression of neuroligin-4 and glycine receptor was unchanged. Increased postsynaptic clustering of gephyrin, without an accompanying increase in GABAergic input or neuroligin-2 and -4 expression, the latter important for clustering of GABA(A) and glycine receptors, respectively, could imply an increased but altered inhibitory connectivity specific for newborn neurons. The changes were transient and expression of both gephyrin and NL-2 was normalized 3 months post-SE. Our findings indicate that seizure-induced brain pathology alters the sub-cellular expression of synaptic adhesion molecules and scaffolding proteins related to particularly inhibitory but also excitatory synapses, which may yield functional consequences for the integration of adult-born neurons. 相似文献
993.
Prey organisms often use multiple sensory cues to gain reliable information about imminent predation threat. In this study we test if a freshwater fish increases the reliance on supplementary cues when the reliability of the primary cue is reduced. Fish commonly use vision to evaluate predation threat, but may also use chemical cues from predators or injured conspecifics. Environmental changes, such as increasing turbidity or water colour, may compromise the use of vision through changes in the optical properties of water. In an experiment we tested if changes in optical conditions have any effects on how crucian carp respond to chemical predator cues. In turbidity treatments we added either clay or algae, and in a brown water colour treatment we added water with a high humic content. We found that carp reduced activity in response to predator cues, but only in the turbidity treatments (clay, algae), whereas the response in the brown water treatment was intermediate, and not significantly different from, clear and turbid water treatments. The increased reliance on chemical cues indicates that crucian carp can compensate for the reduced information content from vision in waters where optical conditions are degraded. The lower effect in brown water may be due to the reduction in light intensity, changes in the spectral composition (reduction of UV light) or to a change in chemical properties of the cue in humic waters. 相似文献
994.
Abrams MB Nilsson I Lewandowski SA Kjell J Codeluppi S Olson L Eriksson U 《PloS one》2012,7(6):e38760
We investigated whether imatinib (Gleevec?, Novartis), a tyrosine kinase inhibitor, could improve functional outcome in experimental spinal cord injury. Rats subjected to contusion spinal cord injury were treated orally with imatinib for 5 days beginning 30 minutes after injury. We found that imatinib significantly enhanced blood-spinal cord-barrier integrity, hindlimb locomotor function, sensorimotor integration, and bladder function, as well as attenuated astrogliosis and deposition of chondroitin sulfate proteoglycans, and increased tissue preservation. These improvements were associated with enhanced vascular integrity and reduced inflammation. Our results show that imatinib improves recovery in spinal cord injury by preserving axons and other spinal cord tissue components. The rapid time course of these beneficial effects suggests that the effects of imatinib are neuroprotective rather than neurorestorative. The positive effects on experimental spinal cord injury, obtained by oral delivery of a clinically used drug, makes imatinib an interesting candidate drug for clinical trials in spinal cord injury. 相似文献
995.
Aims: In this study, the molecular diversity among clones of vancomycin resistant Enterococcus faecium with vanA gene (VRE) is investigated. The aims were to better understand why one clone is predominant in Swedish broiler production and to better assess the potential for zoonotic gene transfer from the different clones. Methods and Results: Twenty‐six isolates were separated into 11 clones. Vancomycin resistance was transferrable from the predominant and five minority clones. Decreased susceptibility to narasin was co‐transferred with vancomycin resistance in four clones, including the predominant. The plasmid addiction system axe‐txe was not detected, and the ω‐ε‐ζ system was detected in one of the minority clones but was not co‐transferred with vancomycin resistance. Conclusions: The results do not explain why one clone is predominant among VRE in Swedish broiler production but confirms the potential for zoonotic spread of vancomycin resistance genes. The near absence of investigated plasmid addiction systems indicates that they do not play an important role in the epidemiology of VRE in Swedish broiler production. The finding that decreased susceptibility to narasin can be co‐transferred with the vanA gene indicates that the use of narasin might play a role in the persistence of vancomycin resistance in enterococci colonizing Swedish broilers. Significance and Impact of the Study: This is, to our knowledge, the first report of transferrable decreased susceptibility to narasin. 相似文献
996.
Anneli M. Ågren Mahsa Haei Peder Blomkvist Mats B. Nilsson Hjalmar Laudon 《Global Change Biology》2012,18(6):1895-1903
Changes in winter time conditions at high‐latitude ecosystems could severely affect the carbon exchange processes. Using a 15 year stream record combined with winter field measurements and laboratory experiment, we studied the regulation of dissolved organic carbon (DOC) concentration in stream water draining boreal mire during snow melt. The most unanticipated finding was that cold soils with deep soil frost resulted in increased snow melt DOC concentrations in the stream runoff. Wintertime field measurements of DOC concentrations below the mire soil frost showed that this phenomenon could be explained by freeze‐out of DOC giving higher levels of DOC in the soil water below the ice as the soil frost developed downwards in the mire. Experimental freezing of water with a certain DOC concentration in the laboratory further corroborated the freeze‐out of DOC. In this experiment, as much as 96% of the DOC was excluded from the ice, whereas the freeze‐out in the mire was less effective (60%). The difference between the proportion of DOC retained in pure water relative to the proportion retained in peat water during freezing is probably due to trapped DOC in the solid peat soil matrix. A simple mass‐balance model showed that to explain the higher stream DOC concentrations during a winter with deep soil frost, approximately 0.5% of the mire area needed to be hydrologically connected to the stream discharge. In the stream records, we also found that the DOC concentrations during snow melt episodic runoff were negatively related to increasing intensity of the snow melt episodes (dilution by low DOC snow melt water) and higher previous export of DOC. 相似文献
997.
Nilsson L Madsen K Topcu SO Jensen BL Frøkiær J Nørregaard R 《American journal of physiology. Renal physiology》2012,302(11):F1430-F1439
Bilateral ureteral obstruction (BUO) in rats is associated with increased cyclooxygenase type 2 (COX-2) expression, and selective COX-2 inhibition prevents downregulation of aquaporins (AQPs) in response to BUO. It was hypothesized that a murine model would display similar changes in renal COX-2 and AQPs upon BUO and that targeted disruption of COX-2 protects against BUO-induced suppression of collecting duct AQPs. COX-2(-/-) and wild-type littermates (C57BL/6) were employed to determine COX-1, -2, AQP2, and AQP3 protein abundances and localization after BUO. In a separate series, sham and BUO wild-type mice were treated with a selective COX-2 inhibitor, parecoxib. The COX-2 protein level increased in wild-type mice in response to BUO and was not detectable in COX-2(-/-). COX-1 protein abundance was increased in sham-operated and BUO mice. Total AQP2 and -3 mRNA and protein levels decreased significantly after BUO in the cortex+outer medulla (C+OM) and inner medulla (IM). The decrease in C+OM AQP2 and -3 levels was attenuated/prevented in COX-2(-/-) mice, whereas there was no change in the IM. In parallel, inhibition of COX-2 by parecoxib rescued C+OM AQP3 and IM AQP2 protein level in wild-type mice subjected to BUO. In summary, 1) In C57BL/6 mice, ureteral obstruction increases renal COX-2 expression in interstitial cells and lowers AQP2/-3 abundance and 2) inhibition of COX-2 activity by targeted disruption or pharmacological blockade attenuates obstruction-induced AQP downregulation. In conclusion, COX-2-derived prostaglandins contribute to downregulation of transcellular water transporters in the collecting duct and likely to postobstruction diureses in the mouse. 相似文献
998.
Kristoffer Sahlholm Johanna Nilsson Daniel Marcellino Kjell Fuxe Peter Århem 《生物化学与生物物理学报:生物膜》2012,1818(12):3081-3089
Agonist potency at some neurotransmitter receptors has been shown to be regulated by voltage, a mechanism which has been suggested to play a crucial role in the regulation of neurotransmitter release by inhibitory autoreceptors. Likewise, receptor deactivation rates upon agonist removal have been implicated in autoreceptor function. Using G protein-coupled potassium (GIRK) channel activation in Xenopus oocytes as readout of receptor activity, we have investigated the voltage sensitivities and signaling kinetics of the hH3445 and hH3365 isoforms of the human histamine H3 receptor, which functions as an inhibitory auto- and heteroreceptor in the nervous system. We have also investigated both the human and the mouse homologues of the related histamine H4 receptor, which is expressed mainly on hematopoietic cells. We found that the hH3445 receptor is the most sensitive to voltage, whereas the hH3365 and H4 receptors are less affected. We further observed a marked difference in response deactivation kinetics between the hH3445 and hH3365 isoforms, with the hH3365 isoform being five to six-fold slower than the hH3445 receptor. Finally, using synthetic agonists, we found evidence for agonist-specific voltage sensitivity at the hH4 receptor. The differences in voltage sensitivities and deactivation kinetics between the hH3445, hH3365, and H4 receptors might be relevant to their respective physiological roles. 相似文献
999.
Eva Schmidt Ola Nilsson Antti Koskela Juha Tuukkanen Claes Ohlsson Bj?rn Rozell Maria Eriksson 《The Journal of biological chemistry》2012,287(40):33512-33522
Hutchinson-Gilford progeria syndrome (HGPS) is a very rare genetic disorder that is characterized by multiple features of premature aging and largely affects tissues of mesenchymal origin. In this study, we describe the development of a tissue-specific mouse model that overexpresses the most common HGPS mutation (LMNA, c.1824C>T, p.G608G) in osteoblasts. Already at the age of 5 weeks, HGPS mutant mice show growth retardation, imbalanced gait and spontaneous fractures. Histopathological examination revealed an irregular bone structure, characterized by widespread loss of osteocytes, defects in mineralization, and a hypocellular red bone marrow. Computerized tomography analysis demonstrated impaired skeletal geometry and altered bone structure. The skeletal defects, which resemble the clinical features reported for bone disease in HGPS patients, was associated with an abnormal osteoblast differentiation. The osteoblast-specific expression of the HGPS mutation increased DNA damage and affected Wnt signaling. In the teeth, irregular dentin formation, as was previously demonstrated in human progeria cases, caused severe dental abnormalities affecting the incisors. The observed phenotype also shows similarities to reported bone abnormalities in aging mice and may therefore help to uncover general principles of the aging process. 相似文献
1000.
While it is accepted that hemopoietic stem cells (HSC) are located in a three-dimensional microenvironment, termed a niche, the cellular and extracellular composition, as well as the multifaceted effects the components of the niche have on HSC regulation, remains undefined. Over the past four decades numerous advances in the field have led to the identification of roles for some cell types and propositions of potentially a number of HSC niches. We present evidence supporting the roles of multiple cell types and extracellular matrix molecules in the HSC niche, as well as discuss the potential significant overlap and intertwining of previously proposed distinct HSC niches. 相似文献