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51.
A set of odours was presented to the housefly Musca domestica and the electrophysiological responses of single olfactory receptor cells in the antennae and palps were recorded. The olfactory cells in the antennae of the housefly showed a large variability of response profiles, but multidimensional cluster analysis suggested a moderate clustering in olfactory response types. Receptor cells with similar or with different odour response profiles can reside in one and the same sensillum. No fixed spatial distribution of olfactory response types over the antennal of palpal surface was found. The odours of 1-octen-3-ol, amyl acetate, 3-methylphenol, 2-pentanone and R(+)limonene elicited the largest responses in antennal cells. Most odours elicited responses in cells of only a few of the clusters, but 1-octen-3-ol was detected by cells of almost all clusters of the antenna. Surprisingly, rather low responses were found to acetic acid, skatole, indole and muscalure, odours that are known to attract flies. Response profiles of palpal cells differed considerably from those of antennal cells. Palpal cells mostly responded to 3-methylphenol and 2-pentanone. In the palps, the clusters of cells responding to 3-methylphenol and 2-pentanone are clearly separated from the other olfactory cells. 相似文献
52.
Hogner A Kastrup JS Jin R Liljefors T Mayer ML Egebjerg J Larsen IK Gouaux E 《Journal of molecular biology》2002,322(1):93-109
Glutamate is the principal excitatory neurotransmitter within the mammalian CNS, playing an important role in many different functions in the brain such as learning and memory. In this study, a combination of molecular biology, X-ray structure determinations, as well as electrophysiology and binding experiments, has been used to increase our knowledge concerning the ionotropic glutamate receptor GluR2 at the molecular level. Five high-resolution X-ray structures of the ligand-binding domain of GluR2 (S1S2J) complexed with the three agonists (S)-2-amino-3-[3-hydroxy-5-(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl]propionic acid (2-Me-Tet-AMPA), (S)-2-amino-3-(3-carboxy-5-methylisoxazol-4-yl)propionic acid (ACPA), and (S)-2-amino-3-(4-bromo-3-hydroxy-isoxazol-5-yl)propionic acid (Br-HIBO), as well as of a mutant thereof (S1S2J-Y702F) in complex with ACPA and Br-HIBO, have been determined. The structures reveal that AMPA agonists with an isoxazole moiety adopt different binding modes in the receptor, dependent on the substituents of the isoxazole. Br-HIBO displays selectivity among different AMPA receptor subunits, and the design and structure determination of the S1S2J-Y702F mutant in complex with Br-HIBO and ACPA have allowed us to explain the molecular mechanism behind this selectivity and to identify key residues for ligand recognition. The agonists induce the same degree of domain closure as AMPA, except for Br-HIBO, which shows a slightly lower degree of domain closure. An excellent correlation between domain closure and efficacy has been obtained from electrophysiology experiments undertaken on non-desensitising GluR2i(Q)-L483Y receptors expressed in oocytes, providing strong evidence that receptor activation occurs as a result of domain closure. The structural results, combined with the functional studies on the full-length receptor, form a powerful platform for the design of new selective agonists. 相似文献
53.
Sylvain Williams Serhiy Souchelnytskyi Marc Danik 《Biochemical and biophysical research communications》2002,290(4):1321-1327
Transforming growth factors betas (TGFbetas) are known to have important roles in neuronal survival and can be upregulated in disease. However, unlike many other trophic factors, nothing is known about the rapid neurotransmitter-like actions of TGFbeta in the CNS. We explored this by examining the effects of TGFbeta on calcium influx of large enzymatically dissociated basal forebrain neurons. We show that brief application of TGFbeta2, but not TGFbeta1, to fura-2AM-loaded neurons reversibly and acutely (within seconds) inhibited K(+)-evoked calcium influx. Moreover, using single-cell RT-PCR, we confirmed that the large TGFbeta2-responsive neurons presented a cholinergic phenotype. Investigation of the signaling mechanism underlying TGFbeta2 actions using whole-cell recordings of calcium currents revealed that TGFbeta2-mediated responses were insensitive to the nonhydrolyzable GTP analogue GTPgammaS. However, TGFbeta2-mediated calcium current reductions were prevented by intracellular perfusion of a Smad2/3 peptide antagonist. Together, these results suggest that TGFbeta2 can acutely regulate the excitability of basal forebrain cholinergic neurons through an atypical signaling mechanism. 相似文献
54.
Baydar T Papp A Aydin A Nagymajtenyi L Schulz H Isimer A Sahin G 《Biological trace element research》2003,92(3):231-244
The present study was undertaken to examine possible aluminum (Al) accumulation in the brain of rats and to investigate whether
subchronic exposure to the metal leads to behavioral and neurophysiological changes in both treated and control groups. Each
of the groups consisted of 10 animals. Aluminum chloride (AlCl3) at a low (50 mg/kg/d) or high (200 mg/kg/d) dose was applied to male Wistar rats by gavage for 8 wk. Al-free water by gavage
was given to the control group throughout the experiment. Behavioral effects were evaluated by open-field (OF) motor activity
and by acoustic startle response (ASR). Electrophysiological examination was done by recording spontaneous activity and sensory-evoked
potentials from the visual, somatosensory, as well as auditory cortex. The Al content of each whole brain was determined by
electrothermal atomic absorption spectrophotometry. Subchronic Al exposure slightly caused some changes in the evoked potentials
and electrocorticograms and in the OF and ASR performance, but these results were not statistically significant. The brain
Al levels of the control and the low and high dose of Al-exposed groups were measured as 0.717±0.208 μg/g (wet weight), 0.963±0.491
μg/g (wet weight) and 1.816±1.157 μg/g (wet weight), respectively. 相似文献
55.
目的探讨应用导管射频消融(RFCA)治疗特发性室性心动过速的疗效。方法经皮穿刺左右侧股静脉右侧股动脉(起源于左室时),将多根6F或7F4极导管送至高位右房(HRA)、房束(HBE)、右室心尖(RVA)、右室流出道(RVOT)或左室(LV),作短阵快速和程序刺激心室诱发VT,同步记录12导联及心腔内各部位电图。结果除1例不能坚持RFCA外,成功11例(91.7%),另1例因疗效不满意改用导管心内膜直流电消融而获成功。结论术前诊断及靶点标测的准确性是RFCA治疗成功的关键。 相似文献
56.
Molecular cloning of GABA transporter-homologous cDNAs from aDrosophila melanogaster headspecific library was accomplished using a conserved oligomer from a highly conserved domain within the mammalian GABA
transporters. Partial DNA sequencing of these cDNAs demonstrated homology with the mammalian transporters, indicating these
are ancient, evolutionarily conserved molecules. Although theDrosophila cDNAs had distinct restriction enzyme patterns, they recognized the same locus inDrosophila genomic DNA, suggesting that the multiple isoforms might arise via alternative splicing. Antibodies specific for the mammalian
GABA transporters GAT1, GAT2 and GAT3 recognized non-overlapping and developmentally distinct patterns of expression inDrosophila neuronal tissues. Treatment of larval instars with nipecotic acid, a generalized GABA reuptake inhibitor, revealed specific,
dose-dependent alterations in behavior consistent with the presence of multiple transporter molecules with differing affinities
for this drug. Synaptic current recordings revealed that nipecotic acid treated larvae have an increase in latency jitter
of evoked quantal release, resulting in a broader average excitatory junctional current which was manifested in a broader
EJP. These results imply that alterations in the development of the CNS occur if GABAergic neurotransmission is protentiated
during development. The data suggest that, as in mammals, there are multiple GABA transporters inDrosophila whose expression is differentially regulated. 相似文献
57.
Kyle Hubbard Phillip Beske Megan Lyman Patrick McNutt 《Journal of visualized experiments : JoVE》2015,(96)
Therapeutic and mechanistic studies of the presynaptically targeted clostridial neurotoxins (CNTs) have been limited by the need for a scalable, cell-based model that produces functioning synapses and undergoes physiological responses to intoxication. Here we describe a simple and robust method to efficiently differentiate murine embryonic stem cells (ESCs) into defined lineages of synaptically active, networked neurons. Following an 8 day differentiation protocol, mouse embryonic stem cell-derived neurons (ESNs) rapidly express and compartmentalize neurotypic proteins, form neuronal morphologies and develop intrinsic electrical responses. By 18 days after differentiation (DIV 18), ESNs exhibit active glutamatergic and γ-aminobutyric acid (GABA)ergic synapses and emergent network behaviors characterized by an excitatory:inhibitory balance. To determine whether intoxication with CNTs functionally antagonizes synaptic neurotransmission, thereby replicating the in vivo pathophysiology that is responsible for clinical manifestations of botulism or tetanus, whole-cell patch clamp electrophysiology was used to quantify spontaneous miniature excitatory post-synaptic currents (mEPSCs) in ESNs exposed to tetanus neurotoxin (TeNT) or botulinum neurotoxin (BoNT) serotypes /A-/G. In all cases, ESNs exhibited near-complete loss of synaptic activity within 20 hr. Intoxicated neurons remained viable, as demonstrated by unchanged resting membrane potentials and intrinsic electrical responses. To further characterize the sensitivity of this approach, dose-dependent effects of intoxication on synaptic activity were measured 20 hr after addition of BoNT/A. Intoxication with 0.005 pM BoNT/A resulted in a significant decrement in mEPSCs, with a median inhibitory concentration (IC50) of 0.013 pM. Comparisons of median doses indicate that functional measurements of synaptic inhibition are faster, more specific and more sensitive than SNARE cleavage assays or the mouse lethality assay. These data validate the use of synaptically coupled, stem cell-derived neurons for the highly specific and sensitive detection of CNTs. 相似文献
58.
59.
60.
Mikala Gabor Klöckners Udo Varadi Maria Eisfeld Jörg Schwartz Arnold Varadi Gyula 《Molecular and cellular biochemistry》1998,185(1-2):95-109
The involvement of cAMP-dependent phosphorylation sites in establishing the basal activity of cardiac L-type Ca2+ channels was studied in HEK 293 cells transiently cotransfected with mutants of the human cardiac 1 and accessory subunits. Systematic individual or combined elimination of high consensus protein kinase A (PKA) sites, by serine to alanine substitutions at the amino and carboxyl termini of the 1 subunit, resulted in Ca2+ channel currents indistinguishable from those of wild type channels. Dihydropyridine (DHP)-binding characteristics were also unaltered. To explore the possible involvement of nonconsensus sites, deletion mutants were used. Carboxyl-terminal truncations of the 1 subunit distal to residue 1597 resulted in increased channel expression and current amplitudes. Modulation of PKA activity in cells transfected with the wild type channel or any of the mutants did not alter Ca2+ channel functions suggesting that cardiac Ca2+ channels expressed in these cells behave, in terms of lack of PKA control, like Ca2+ channels of smooth muscle cells. 相似文献