全文获取类型
收费全文 | 3478篇 |
免费 | 141篇 |
国内免费 | 45篇 |
专业分类
3664篇 |
出版年
2024年 | 3篇 |
2023年 | 38篇 |
2022年 | 58篇 |
2021年 | 45篇 |
2020年 | 56篇 |
2019年 | 83篇 |
2018年 | 83篇 |
2017年 | 65篇 |
2016年 | 66篇 |
2015年 | 87篇 |
2014年 | 159篇 |
2013年 | 223篇 |
2012年 | 90篇 |
2011年 | 124篇 |
2010年 | 98篇 |
2009年 | 106篇 |
2008年 | 136篇 |
2007年 | 183篇 |
2006年 | 162篇 |
2005年 | 146篇 |
2004年 | 174篇 |
2003年 | 158篇 |
2002年 | 132篇 |
2001年 | 78篇 |
2000年 | 71篇 |
1999年 | 92篇 |
1998年 | 91篇 |
1997年 | 91篇 |
1996年 | 82篇 |
1995年 | 78篇 |
1994年 | 81篇 |
1993年 | 62篇 |
1992年 | 64篇 |
1991年 | 70篇 |
1990年 | 53篇 |
1989年 | 51篇 |
1988年 | 45篇 |
1987年 | 46篇 |
1986年 | 31篇 |
1985年 | 23篇 |
1984年 | 13篇 |
1983年 | 10篇 |
1982年 | 17篇 |
1981年 | 13篇 |
1980年 | 2篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1977年 | 6篇 |
1976年 | 6篇 |
1975年 | 4篇 |
排序方式: 共有3664条查询结果,搜索用时 0 毫秒
91.
Verónica Alvarez Maubecin Viviana N. Sanchez Marcelo D. Rosato Siri Bruce D. Cherksey Mutzuyuki Sugimori Rodolfo Llinás Osvaldo D. Uchitel 《Journal of neurochemistry》1995,64(6):2544-2551
Abstract: The voltage-dependent calcium channels present in mammalian and chicken brain synaptosomes were characterized pharmacologically using specific blockers of L-type channels (1,4-dihydropyridines), N-type channels (ω-conotoxin GVIA), and P-type channels [funnel web toxin (FTX) and ω-agatoxin IVA]. K+-induced Ca2+ uptake by chicken synaptosomes was blocked by ω-conotoxin GVIA (IC50 = 250 nM). This toxin at 5 µM did not block Ca2+ entry into rat frontal cortex synaptosomes. FTX and ω-agatoxin IVA blocked Ca2+ uptake by rat synaptosomes (IC50 = 0.17 µl/ml and 40 nM, respectively). Likewise, in chicken synaptosomes, FTX and ω-agatoxin IVA affected Ca2+ uptake. FTX (3 µl/ml) exerted a maximal inhibition of 40% with an IC50 similar to the one obtained in rat preparations, whereas with ω-agatoxin IVA saturation was not reached even at 5 µM. In chicken preparations, the combined effect of saturating concentrations of FTX (1 µl/ml) and different concentrations of ω-conotoxin GVIA showed no additive effects. However, the effect of saturating concentrations of FTX and ω-conotoxin GVIA was never greater than the one observed with ω-conotoxin GVIA. We also found that 60% of the Ca2+ uptake by rat and chicken synaptosomes was inhibited by ω-conotoxin MVIID (1 µM), a toxin that has a high index of discrimination against N-type channels. Conversely, nitrendipine (10 µM) had no significant effect on Ca2+ uptake in either the rat or the chicken. In conclusion, Ca2+ uptake by rat synaptosomes is potently inhibited by different P-type Ca2+ channel blockers, thus indicating that P-type channels are predominant in this preparation. In contrast, Ca2+ uptake by chicken synaptosomes is sensitive to ω-conotoxin GVIA, FTX, ω-agatoxin IVA, and ω-conotoxin MVIID. This suggests that a channel subtype with a mixed pharmacology is present in chicken synaptosomes. 相似文献
92.
Abstract: Calcium acts as a second messenger and can enter neurons through several types of calcium channel. We sought to determine whether the calcium-dependent mechanisms inducing c- fos expression are identical following activation, by appropriate drugs, of L-type voltage-sensitive calcium channels or NMDA and non-NMDA receptors or following inhibition of the GABAergic system. We used primary cortical neurons and OF1 mice, and the levels of c- fos protein and c- fos mRNA were detected after treatment with the drugs by means of immunocytochemistry and in situ hybridization. The calmodulin antagonist N -(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) abolished γ-hexachlorocyclohexane-, Bay K 8644-, pentylenetetrazole-, and kainic acid-induced increases in c- fos expression in cultured neurons. Conversely, W-7 did not affect either NMDA- or picrotoxinin-mediated increases in c- fos expression. In mice, the pattern of protooncogene expression displayed some differences compared with cultured neurons, depending on the treatment. W-7 administered before γ-hexachlorocyclohexane, Bay K 8644, or pentylenetetrazole blocked the expression of c- fos elicited by these compounds. However, W-7 was not able to abolish c- fos expression induced by picrotoxinin. In the animals treated with W-7 before kainic acid or NMDA administration, c- fos expression was inhibited in cerebral cortex, but it was still present in hippocampus. These results agree with the existence of diverse mechanisms transducing the calcium signals to the nucleus. Calmodulin may mediate neuronal responses depending on the route by which calcium enters the neuron, resulting in activation of different enzymes. 相似文献
93.
Electrophysiological properties of mouse bone marrow-derived mast cells (BMMC) were studied under the whole-cell clamp configuration. About one third of the cells were quiescent, but others expressed either inward or outward currents. Inwardly rectifying (IR) currents were predominant in 14% of the cells, and outwardly rectifying (OR) currents in 24%. The rest (22%) of the cells exhibited both inward and outward currents. The IR currents were eliminated by 1 mm Ba2+, and were partially inhibited by 100 μm quinidine. The reversal potential was dependent on extracellular K+, thereby indicating that K+ mediated the IR currents. The negative conductance region was seen at potentials positive to E K. The OR currents did not apparently depend on the extracellular K+ concentration, but were reduced by lowering the extracellular Cl? concentration. The OR currents were partially blocked by 1 mm Ba2+, and were further blocked by a Cl? channel blocker, 4,4′-diisothiocyano-2, 2′-stilbenedisulfonate (DIDS). In addition, the reversal potential of the OR currents was positively shifted by decreasing the ratio of external and internal Cl? concentrations, suggesting that Cl? was a major ion carrier. In cells exhibiting IR currents, the membrane potential varied among cells and tended to depolarize by elevating the external K+ concentration. In cells with OR currents, the resting potential was hyperpolarized in association with an increase in conductance. These results suggest that BMMC have a heterogeneous electrophysiological profile that may underlie a variety of ion channels expressed in different phenotypes of mast cells. Activities of both the inwardly rectifying K+ channel and the outwardly rectifying Cl? channel seem to contribute to the regulation of the membrane potential. 相似文献
94.
Whole-cell patch clamp recordings were done on giant protoplasts of Escherichia coli. The pressure sensitivity of the protoplasts was studied. Two different unit conductance mechanosensitive channels, 1100 ± 25 pS and 350 ± 14 pS in 400 mm symmetric KCl solution, were observed upon either applying positive pressure to the interior of the cells or down shocking the cells osmotically. The 1100 pS conductance channel discriminated poorly among the monovalent ions tested and it was permeable to Ca2+ and glutamate?. Both of the two channels were sensitive to the osmotic gradient across the membrane; the unit conductances of the channels remained constant while the mean current of the cell was increased by increasing the osmotic gradient. Both of the channels were voltage sensitive. Voltage-ramp results showed that the pressure sensitivity of protoplasts was voltage dependent: there were more channels active upon depolarization than hyperpolarization. The mech anosensitive channels were reversibly blocked by gadolinium ion. Also they could reversibly be inhibited by protons. Mutations in two of the potassium efflux systems, KefB and KefC, did not affect the channel activity, while a null mutation in the gene for KefA changed the channel activity significantly. This indicates a potential modulation of these channels by KefA. 相似文献
95.
F. K. Ghishan S. Knobel J. A. Barnard M. Breyer 《The Journal of membrane biology》1995,143(3):267-271
Aquaporin CHIP, a 28 kDa channel forming protein, has been proposed to function as water channel in both erythrocyte and kidney proximal tubule. Recently, we have reported that in frog urinary bladder, a model of the kidney collecting tubule, polyclonal antibodies against human erythrocyte CHIP recognize and immunoprecipitate a 30 kDa protein from the epithelial cell homogenate. In the present work confocal fluorescence microscopy was used to determine the cellular and subcellular localization of CHIP28-like proteins in the urinary epithelium. A clear labeling of the apical border was found after Triton X-100 permeabilization. The labeling was distributed throughout the apical domain and not restricted to specific domains of the membrane. The staining was also present in the deeper confocal sections where the fluorescence seems to be localized at the cellular contour. No difference in the labeling patterns was observed between resting and ADH-treated bladder. Specificity of the staining was confirmed by the absence of the labeling pattern when antiserum was preadsorbed on CHIP28 protein immobilized on Immobilon P stripes. Our results suggest that CHIP-like proteins are not proteins inserted in the apical membrane during the antidiuretic response. Moreover, we do not know whether the labeling was due to the presence of CHIP28 itself or an as-yet-unidentified protein sharing immunological analogies with aquaporin CHIP. 相似文献
96.
Patch clamp techniques were used to record whole cell and single channel Na+ currents from NB41A3 neuroblastoma cells grown in culture. Cells were grown for two weeks in control medium or medium supplemented with 30 mm
d-glucose of 30 mm l-fucose.Cells exposed to glucose or l-fucose had smaller whole cell Na+ currents than cells grown in unsupplemented medium, consistent with earlier studies (Yorek, Stefani & Wachtel, 1994). Whole cell macroscopic currents showed no change in activation or inactivation kinetics. Single channel current properties and opening probability were also unchanged.The number of [3H]saxitoxin binding sites, and therefore the total number of Na+ channels, was not reduced in cells grown in glucose or l-fucose (Yorek et al., 1994). Therefore, we conclude that some of the channels must have been rendered nonfunctional by the conditioning media. The finding that single channel properties are not altered suggests that channels become nonfunctional in an all-or-none manner.This work was supported by Merit Review Awards to M.A. Yorek and R.E. Wachtel from the Department of Veterans Affairs and by National Institutes of Health grant DK45453 to M.A. Yorek. 相似文献
97.
Abstract: Galactosylceramide ("galactocerebroside"; GalC) is a major glycolipid in the myelin sheath of the CNS and the PNS. The enzyme UDP-galactose:ceramide galactosyltransferase (CGalT) catalyzes the final step of the synthesis of GalC: the transfer of galactose to ceramide. By a differential screening approach, we have isolated a cDNA, the sequence of which is identical to the recently isolated cDNA clones for CGalT. By northern analysis and in situ hybridization we demonstrated that CGalT mRNA is expressed at birth in oligodendrocytes and Schwann cells, an expression pattern corresponding to the onset of myelination. In addition to the high expression levels of CGalT in oligodendrocytes and Schwann cells, in situ hybridization also showed expression in subtypes of neurons in spinal cord, cerebellum, and brainstem in the adult CNS, but at a much lower level than in oligodendrocytes. Expression of CGalT in COS cells demonstrated that CGalT has a preference for hydroxyceramide as a substrate. CGalT-expressing COS cells synthesize and transport GalC to their cell surface as shown by immunofluorescence and by lipid analysis of living cells. Our results suggested that the CGalT specifically uses hydroxyceramide for the synthesis of GalC and that separate (co)enzymes are not needed. 相似文献
98.
99.
Block by 5-hydroxytryptamine of neuronal acetylcholine receptor channels expressed inXenopus oocytes
Summary 1. Effects of 5-hydroxytryptamine (5-HT) on neuronal nicotinic acetylcholine (ACh) receptor channels were investigated by expressing cloned channel subunits inXenopus oocytes.2. When channels were expressed with a combination of
3 and
4 subunits, 5-HT (10 to 300 µM) reversibly inhibited an inward current activated by 100 µM ACh in a concentration-dependent manner. The inhibition was also observed when
3 subunit was combined with
2 subunit instead of
4 subunit, or
4 subunit was combined with
2 or
4–1 subunit instead of
3 subunit to express channels.3. Compounds known to antagonize at 5-HT receptors (LY53857, metoclopramide and propranolol) exhibited an agonistic effect: they inhibited the ACh-activated current.4. The results suggest that 5-HT inhibits recombinant neuronal nicotinic receptor channels through a binding-site distinct from conventional 5-HT receptors. The binding-site may not be attributed to a unique type of channel subunits. 相似文献
100.
Mercurial-sensitive water transport in barley roots 总被引:16,自引:0,他引:16
Masashi Tazawa Eiji Ohkuma Mineo Shibasaka Susumu Nakashima 《Journal of plant research》1997,110(4):435-442
An isolated barley root was partitioned into the apical and basal part across the partition wall of the double-chamber osmometer.
Transroot water movement was induced by subjecting the apical part to a sorbitol solution, while the basal part with the cut
end was in artificial pond water. The rate of transroot osmosis was first low but enhanced by two means, infilitration of
roots by pressurization and repetition of osmosis. Both effects acted additively. The radial hydraulic conductivity (Lpr) was calculated by dividing the initial flow rate with the surface area of the apical part of the root, to which sorbitol
was applied, and the osmotic gradient between the apical and basal part of the root. Lpr which was first 0.02–0.04 pm s−1 Pa−1 increased up to 0.25–0.4 pm s−1 Pa−1 after enhancement. Enhancement is assumed to be caused by an increase of the area of the plasma membrane which is avallable
to osmotic water movement. The increased Lpr is in the same order of magnitude as the hydraulic conductivity (Lp) of epidermal and cortical cells of barley roots obtained
by Steudie and Jeschke (1983). HgCl2, a potent inhibitor of water channels, suppressed Lpr of non-infiltrated and infiltrated roots down to 17% and 8% of control values, respectively. A high sensitivity of Lpr to HgCl2 suggests that water channels constitute the most conductive pathway for osmotic radial water movement in barley roots. 相似文献