全文获取类型
收费全文 | 10648篇 |
免费 | 901篇 |
国内免费 | 339篇 |
专业分类
11888篇 |
出版年
2024年 | 32篇 |
2023年 | 89篇 |
2022年 | 149篇 |
2021年 | 153篇 |
2020年 | 282篇 |
2019年 | 347篇 |
2018年 | 383篇 |
2017年 | 308篇 |
2016年 | 296篇 |
2015年 | 356篇 |
2014年 | 490篇 |
2013年 | 663篇 |
2012年 | 305篇 |
2011年 | 485篇 |
2010年 | 338篇 |
2009年 | 378篇 |
2008年 | 466篇 |
2007年 | 503篇 |
2006年 | 447篇 |
2005年 | 441篇 |
2004年 | 409篇 |
2003年 | 382篇 |
2002年 | 342篇 |
2001年 | 208篇 |
2000年 | 244篇 |
1999年 | 259篇 |
1998年 | 257篇 |
1997年 | 285篇 |
1996年 | 218篇 |
1995年 | 226篇 |
1994年 | 181篇 |
1993年 | 186篇 |
1992年 | 204篇 |
1991年 | 176篇 |
1990年 | 166篇 |
1989年 | 157篇 |
1988年 | 138篇 |
1987年 | 134篇 |
1986年 | 85篇 |
1985年 | 123篇 |
1984年 | 134篇 |
1983年 | 84篇 |
1982年 | 94篇 |
1981年 | 74篇 |
1980年 | 68篇 |
1979年 | 73篇 |
1978年 | 21篇 |
1977年 | 13篇 |
1976年 | 16篇 |
1975年 | 8篇 |
排序方式: 共有10000条查询结果,搜索用时 14 毫秒
21.
The assembly of high voltage-activated Ca2+ channels with different β subunits influences channel properties and possibly subcellular targeting. We studied β subunit expression in the somata and axon terminals of the magnocellular neurosecretory cells, which are located in the supraoptic nucleus (SON) and neurohypophysis, respectively. Antibodies directed against the 4 CaVβ subunits (CaVβ1-CaVβ4) were used for immunoblots and for immunostaining of slices of these two tissues. We found that all 4 β subunits are expressed in both locations, but that CaVβ2 had the highest relative expression in the neurohypophysis. These data suggest that the CaVβ2 subunit is selectively targeted to axon terminals and may play a role in targeting and/or regulating the properties of Ca2+ channels. 相似文献
22.
Rajabrata Bhuyan 《Journal of biomolecular structure & dynamics》2017,35(2):380-398
The voltage gated Kv1.5 channels conduct the ultrarapid delayed rectifier current (IKur) and play critical role in repolarization of action potential duration. It is the most rapidly activated channel and has very little or no inactivated states. In human cardiac cells, these channels are expressed more extensively in atrial myocytes than ventricle. From the evidences of its localization and functions, Kv1.5 has been declared a selective drug target for the treatment of atrial fibrillation (AF). In this present study, we have tried to identify the rapidly activating property of Kv1.5 and studied its mode of inhibition using molecular modeling, docking, and simulation techniques. Channel in open conformation is found to be stabilized quickly within the dipalmitoylphosphatidylcholine membrane, whereas most of the secondary structure elements were lost in closed state conformation. The obvious reason behind its ultra-rapid property is possibly due to the amino acid alteration in S4–S5 linker; the replacement of Lysine by Glutamine and vice versa. The popular published drugs as well as newly identified lead molecules were able to inhibit the Kv1.5 in a very similar pattern, mainly through the nonpolar interactions, and formed sable complexes. V512 is found as the main contributor for the interaction along with the other important residues such as V505, I508, A509, V512, P513, and V516. Furthermore, two screened novel compounds show surprisingly better inhibitory potency and can be considered for the future perspective of antiarrhythmic survey. 相似文献
23.
Hiroshi Monoi 《生物化学与生物物理学报:生物膜》1982,693(1):159-164
An electrostatic calculation suggests that when an ion is bound near the mouth of a channel penetrating a low-dielectric membrane, a counter ion may form an ion pair with this ion. The tendency towards ion-pair formation is remarkably enhanced at channel mouths by forces (image forces) arising from the charges induced on the boundaries between different dielectrics. The binding constant for the formation of ion-pairs of monovalent ions is estimated under the assumption that local interactions between the counter ion and the channel wall are negligibly small. It is of the order of 1–10 molal?1 or more for the binding of a Cl? (F?) counter ion to an () ion if appropriate conditions are fulfilled. The binding constant depends on the position of the binding site, the dimensions and geometries of the channel and channel mouth, and the state of ion loading of the channel, as well as the ionic species. The present results also indicate that when cation (anion) channels have anionic (cationic) groups as integrant parts of their channel walls, interactions between these charged groups and permeant ions are markedly enhanced by the image forces. 相似文献
24.
The reference intervals for biochemical variables and red blood cell indices of healthy intensively bred channel catfish Ictalurus punctatus were determined. The blood variables were determined using standardized clinical methods. The reference intervals (25th and 75th percentiles) were established using a non-parametric method. Reference intervals for plasma glucose, serum total protein, sodium, potassium, calcium, magnesium, chloride concentration, primary and secondary red blood cell indices were established. The haematological and biochemical reference intervals established may allow important clinical decisions about channel catfish. 相似文献
25.
Using an insoluble inorganic salt precipitation technique, the permeability of cell walls and especially of endodermal Casparian bands (CBs) for ions was tested in young roots of corn (Zea mays) and rice (Oryza sativa). The test was based on suction of either 100 µm CuSO4 or 200 µm K4[Fe(CN)6] into the root from its medium using a pump (excised roots) or transpirational stream (intact seedlings), and subsequent perfusion of xylem of those root segments with the opposite salt component, which resulted in precipitation of insoluble brown crystals of copper ferrocyanide. Under suction, Cu2+ could cross the endodermis apoplastically in both plant species (although at low rates) developing brown salt precipitates in cell walls of early metaxylem and in the region between CBs and functioning metaxylem vessels. Hence, at least Cu2+ did cross the endodermis dragged along with the water. The results suggested that CBs were not perfect barriers to apoplastic ion fluxes. In contrast, ferrocyanide ions failed to cross the mature endodermis of both corn and rice at detectable amounts. The concentration limit of apoplastic copper was 0.8 µm at a perfusion with 200 µm K4[Fe(CN)6]. Asymmetric development of precipitates suggested that the cation, Cu2+, moved faster than the anion, [Fe(CN)6]4–, through cell walls including CBs. Using Chara cell wall preparations (‘ghosts’) as a model system, it was observed that, different from Cu2+, ferrocyanide ions remained inside wall-tubes suggesting a substantially lower permeability of the latter which agreed with the finding of an asymmetric development of precipitates. In both corn and rice roots, there was a significant apoplastic flux of ions in regions where laterals penetrated the endodermis. Overall, the results show that the permeability of CBs to ions is not zero. CBs do not represent a perfect barrier for ions, as is usually thought. The permeability of CBs may vary depending on growth conditions which are known to affect the intensity of formation of bands. 相似文献
26.
Bruce Cornell 《Journal of bioenergetics and biomembranes》1987,19(6):655-676
Gramicidin A forms ion-conducting channels which can traverse the hydrocarbon core of lipid bilayer membranes. The structures formed by gramicidin A are among the best characterized of all membrane-bound polypeptides or proteins. In this review a brief summary is given of the occurrence, conformation, and synthesis of gramicidin A, and of its use as a model for ion transport and the interaction of proteins and lipids in biological membranes. 相似文献
27.
A. Coulombe H. Duclohier E. Coraboeuf N. Touzet 《European biophysics journal : EBJ》1987,14(3):155-162
Large conductance channels were observed in the membrane of cultured cardiac cells of newborn rats studied with the patch-clamp technique in cell-attached and inside-out configurations. These channels were observed in 4% of the patches. In the cell-attached configuration they exhibited outward rectification and partial inactivation. In the inside-out configuration no rectification occurred but inactivation was present, mainly during hyperpolarizations. Two channels with large single unit conductances (400–450 pS) and one with a smaller conductance (200–250 pS) were frequently observed in the same patch. The two large channels generally had different kinetics. Under steady-state conditions the opening probability of the faster channel appeared to be voltage-independent. The slower channel was activated by depolarization. In asymmetrical solutions the permeability ratios P
Na/P
Cl were 0.03 and 0.24 for the larger and smaller channels, respectively; corresponding values for P
Ba/P
Cl were 0.04 and 0.09. It is proposed that in cardiac membranes the chloride permeability system is composed of widely dispersed microclusters forming grouped channels of different types and sizes. 相似文献
28.
D. T. Edmonds 《European biophysics journal : EBJ》1987,14(4):195-201
Most current models of membrane ion channel gating are abstract compartmental models consisting of many undefined states connected by rate constants arbitrarily assigned to fit the known kinetics. In this paper is described a model with states that are defined in terms of physically plausible real systems which is capable of describing accurately most of the static and dynamic properties measured for the sodium channel of the squid axon. The model has two components. The Q-system consists of charges and dipoles that can move in response to an electric field applied across the membrane. It would contain and may compose the gating charge that is known to transfer prior to channel opening. The N-system consists of a charged group or dipole that is constrained to move only in the plane of the membrane and thus does not interact directly with the trans-membrane electric field but can interact electrostatically with the Q-system. The N-system has only two states, its resting state (channel closed) and its excited state (channel open) and its response time is very short in comparison with that of the Q-system. On depolarizing the membrane the the N-system will not make a transition to its open state until a critical amount of Q-charge transfer has occurred. Using only four adjustable parameters that are fully determined by fitting the equilibrium properties of the model to those of the sodium channel in the squid axon, the model is then able to describe with some accuracy the kinetics of channel opening and closing and includes the Cole and Moore delay. In addition to these predictions of the behaviour of assemblies of channels the model predicts some of the individual channel properties measured by patch clamp techniques. 相似文献
29.
Activation of Dopamine Receptors Does Not Affect Phosphoinositide Turnover in NCB-20 Cells 总被引:1,自引:1,他引:0
Dopamine inhibits and serotonin stimulates adenylate cyclase activity in a neuroblastoma X Chinese hamster brain explant cell line (NCB-20). The inhibition of cyclic AMP accumulation by dopamine was blocked by pretreatment of the cells with pertussis toxin. Carbachol and bradykinin stimulated the accumulation of water-soluble inositol phosphates whereas thyrotropin-releasing hormone, vasopressin, neurotensin, and phenylephrine were without effect. Dopamine and serotonin had no significant effect on carbachol-induced phosphoinositide hydrolysis or the levels of the parent lipids within the membrane. Forskolin induced a much larger stimulation of cyclic AMP than did serotonin, and caused an increase in the levels of phosphatidylinositol-4-phosphate and phosphatidyl inositol-4,5-bisphosphate in the cell membrane. 相似文献
30.
María Sitges† Lourival Domingos Possani‡ Alejandro Bayón† 《Journal of neurochemistry》1987,48(6):1745-1752
Toxic peptides II-9.2.2 and II-10, purified from Centruroides noxius venom, bear highly homologous N-terminal amino acid sequences, and both toxins are lethal to mice. However, only toxin II-10 is active on the voltage-clamped squid axon, selectively decreasing the voltage-dependent Na+ current. Here, we have tested toxins II-9 and II-10 on synaptosomes from mouse brain: both toxins increased the release of gamma-[3H]aminobutyric acid ([3H]GABA). Their effect was completely blocked by tetrodotoxin or by the absence of external Na+. Also, both toxins increased Na+ permeability in isolated nerve terminals. Besides the observation that toxin II-9 is active on synaptosomes, the effect of toxin II-10 in this preparation is opposite to that observed in the squid axon. Thus, our results reflect functional differences between the populations of Na+ channels in mouse brain synaptosomes and in the squid axon. The release of GABA evoked by these toxins from synaptosomes required external Ca2+ and was blocked by Ca2+ channel blockers (verapamil and Co2+). This latter observation is in sharp contrast to the releasing action of veratrine, which evoked release even in the absence of external Ca2+. Furthermore, the action of both C. noxius toxins was potentiated by veratrine, a result suggesting they have different mechanisms of action. Among drugs that release neurotransmitters by increasing Na+ permeability, it is noteworthy that scorpion toxins are the only ones yet reported to have a strict requirement for external Ca2+. 相似文献