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981.
Extracellular nucleotides exert autocrine/paracrine effects on ion transport by activating P2 receptors. We studied the effects of extracellular ATP and UTP on the cystic fibrosis transmembrane conductance regulator (CFTR) channel stably expressed in Chinese Hamster Ovary cells (CHO-BQ1 cells). CFTR activity was measured using the (125I) iodide efflux technique and whole-cell patch-clamp recording in response to either forskolin or xanthine derivatives. Using RT-PCR and intracellular calcium concentration ([Ca2+]i) measurement, we showed that CHO-BQ1 cells express P2Y2 but not P2Y4 receptors. While ATP and UTP induced similar increases in [Ca2+]i, pre-addition by one of these two agonists desensitized the response for the other, suggesting that ATP- and UTP-induced [Ca2+]i increases were mediated by a common receptor, which was identified as the P2Y2 subtype. CFTR activity was reduced by ATP and UTP but not by ADP or adenosine applications. This inhibitory effect of ATP on CFTR activity was not due to a change in cAMP level. Furthermore, CFTR activation by forskolin or IBMX failed to promote [Ca2+]i increase, suggesting that CFTR activation did not generate an ATP release large enough to stimulate P2Y2 receptors. Taken together, our results show that endogenous P2Y2 receptor activation downregulates CFTR activity in a cAMP-independent manner in CHO cells.
B. Marcet and V. Chappe contributed equally to this work. 相似文献
982.
Dof is a large molecule essential for signal transduction by the two FGF receptors in Drosophila. It contains two ankyrin repeats and a coiled-coil region, but has no other recognisable structural motif. Dof shares these features with its closest vertebrate relatives, the B-cell signalling molecules BCAP and BANK. In addition, this family of proteins shares a region of homology upstream of the ankyrin repeats, which we call the Dof/BCAP/BANK (DBB) motif. We have identified 44 proteins that interact with Dof in a yeast two-hybrid screen. These include the Drosophila FGF-receptor Heartless and Dof itself. We show that the integrity of the DBB motif is required both for Dof and for BCAP to form dimers. Analysis of the interactions between a set of deletion constructs of Dof and the panel of interactors suggests that Dof may adopt different conformations, with a folded conformation stabilized by interactions between the DBB motif and the C-terminal part of the protein. 相似文献
983.
Differential effects of stretch and compression on membrane currents and [Na+]c in ventricular myocytes 总被引:1,自引:0,他引:1
Isenberg G Kazanski V Kondratev D Gallitelli MF Kiseleva I Kamkin A 《Progress in biophysics and molecular biology》2003,82(1-3):43-56
Mechano-electrical feedback was studied in the single ventricular myocytes. A small fraction (approximately 10%) of the cell surface could be stretched or compressed by a glass stylus. Stretch depolarised, shortened the action potential and induced extra systoles. Stretch activated non-selective cation currents (Ins) showed a linear voltage dependence, a reversal potential of 0 mV, a pure cation selectivity, and were blocked by 8 μM Gd3+ or 30 μM streptomycin. Stretch reduced Ca2+ and K+ (IK) currents. Local compression of broadwise attached cells activated IK but not Ins. Cytochalasin D or colchicin, thought to disrupt the cytoskeleton, suppressed the mechanosensitivity of Ins and IK. During stretch, the cytosolic sodium concentration increased with spatial heterogeneities, local hotspots with [Na+]c>24 mM appeared close to surface membrane and t-tubules (pseudoratiometric imaging using Sodium Green fluorescence). Electronprobe microanalysis confirmed this result and indicated that stretch increased total sodium [Na] in cell compartments such as mitochondria, nuclear envelope and nucleus. Our results obtained by local stretch differ from those obtained by end-to-end stretch (literature). We speculate that channels may be activated not only by axial but also by shear stress, and, that stretch can activate channels outside the deformed sarcomeres via second messenger. 相似文献
984.
Carotenoid-based colours are widespread in animals and are used as signals in intra- and interspecific communication. In nestling birds, the carotenoids used for feather pigmentation may derive via three pathways: (1) via maternal transfer to egg yolk; (2) via paternal feeds early after hatching when females are mainly brooding; or (3) via feeds from both parents later in nestling life. We analysed the relative importance of the proposed carotenoid sources in a field experiment on great tit nestlings (Parus major). In a within-brood design we supplemented nestlings with carotenoids shortly after hatching, later on in the nestling life, or with a placebo. We show that the carotenoid-based colour expression of nestlings is modified maximally during the first 6 days after hatching. It reveals that the observed variation in carotenoid-based coloration is based only on mechanisms acting during a short period of time in early nestling life. The experiment further suggests that paternally derived carotenoids are the most important determinants of nestling plumage colour. 相似文献
985.
Ionic and pH signalling from roots to shoots of flooded tomato plants in relation to stomatal closure 总被引:6,自引:1,他引:5
Jackson Michael B. Saker Leslie R. Crisp Carol M. Else Mark A. Janowiak Franciszek 《Plant and Soil》2003,253(1):103-113
Soil flooding damages shoot systems by inhibiting root functioning. An example is the inhibition of water uptake brought about by decreased root hydraulic conductance. The extent of any resulting foliar dehydration this causes is limited by partial stomatal closure that begins within 4 h and is maintained for several days. Root to shoot signals that promote closure in flooded tomato plants have remained elusive but may include changes in solute delivery to the shoot by transpiration. Accordingly, we examined total osmolites and selected mineral ions in samples of xylem sap flowing at rates approximating whole plant transpiration. After 2.5 h flooding,delivery of total osmolites and of PO4
3-SO4
2-Ca2+K+NO3
– and H+strongly decreased while Na+ remained excluded. Several hours later, deliveries of osmolites, PO4
3-, SO4
2-, Ca2+, and Na+ rose above control values, suggesting that, after approximately 10 h, root integrity became degraded and solute uptake de-regulated. Deliveries of NO3
– remained below control values. Reducing or eliminating the supply of K+ to detached leaves to test the potential of decreased K+ delivery to close stomata proved negative. Decrease in H+ delivery was associated with sap alkalisation. However, raising the pH of buffer from 6.0 or 6.5 to 7.0 did not close stomata when tested in the presence of abscisic acid (ABA) at a concentration (10 mol m–3) typical of the transpiration stream of flooded plants. It is concluded that despite their rapidity and scale, negative messages in the form of increased pH and decreased solute delivery from roots to shoots are, themselves, unlikely initiators of stomatal closure in flooded tomato plants. 相似文献
986.
Wisniewski TP Tanzi CL Gindhart JG 《Biology of the cell / under the auspices of the European Cell Biology Organization》2003,95(9):595-602
The microtubule-based motor kinesin-I is essential for the intracellular transport of membrane-bound organelles in the Drosophila nervous system and female germ line. A number of studies have demonstrated that kinesin-I binds to its intracellular cargos through protein-protein interactions between the kinesin tail domain and proteins on the cargo surface. To identify proteins that mediate or regulate kinesin-cargo interactions, we have performed yeast two-hybrid screens of a Drosophila embryonic cDNA library, using the tetratricopeptide repeats of the kinesin light chain and amino acids 675-975 of the kinesin heavy chain as baits. One of the proteins we have identified is YETI. Interestingly, YETI has the unique ability to bind specifically to both subunits of the kinesin tail domain. An epitope-tagged YETI fusion protein, when expressed in Drosophila S2 cultured cells, binds to kinesin-I in copurification assays, suggesting that YETI-kinesin-I interactions are context-independent. Immunostaining of cultured cells expressing YETI shows that YETI accumulates in the nucleus and cytosol. YETI is evolutionarily conserved, and its yeast homolog (AOR1) may have a role in regulating cytoskeletal dynamics or intracellular transport. Collectively, these results demonstrate that YETI interacts with both kinesin subunits of the kinesin tail domain, and is potentially involved in kinesin-dependent transport pathways. 相似文献
987.
The hepatitis C virus persistence: how to evade the immune system? 总被引:14,自引:0,他引:14
Hepatitis C virus (HCV) is an emerging virus of medical importance. A majority of HCV infections become chronic and lead to chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV usually induces robust immune responses, but it frequently escapes the immune defense to establish persistent infection. The fact that HCV exists as an evolving quasispecies plays an important role in the selection of escape mutants. Furthermore, several viral proteins interfere with cellular functions, in particular, those involved in the immune response of the host. Several HCV proteins also modulate cell signalling through interaction with different effectors involved in cell proliferation and apoptosis, or in the interferon-signalling pathway. In addition, HCV infects immune cells such as B and T cells, and thus affects their normal functions. These various strategies used by HCV to counter the immune response of the host are reviewed here. A better understanding of these mechanisms would help design new therapeutic targets. 相似文献
988.
Heck S Grau T Buchala A Métraux JP Nawrath C 《The Plant journal : for cell and molecular biology》2003,36(3):342-352
The salicylic acid (SA)-induction deficient (sid) mutants of Arabidopsis, eds5 and sid2 accumulate normal amounts of camalexin after inoculation with Pseudomonas syringae pv. tomato (Pst), while transgenic NahG plants expressing an SA hydroxylase that degrades SA have reduced levels of camalexin and exhibit a higher susceptibility to different pathogens compared to the sid mutants. SID2 encodes an isochorismate synthase necessary for the synthesis of SA. NahG was shown to act epistatically to the sid mutant phenotype regarding accumulation of camalexin after inoculation with Pst in eds5NahG and sid2NahG plants. The effect of the pad4 mutation on the sid mutant phenotype was furthermore tested in eds5pad4 and sid2pad4 double mutants, and it was demonstrated that PAD4 acts epistatically to EDS5 and SID2 regarding the production of camalexin after inoculation with Pst. NahG plants and pad4 mutants were also found to produce less ethylene (ET) after infection with Pst in comparison to the wild type (WT) and sid mutants. Both PAD4 and NahG acted epistatically to SID regarding the Pst-dependent production of ET that was found to be necessary for the accumulation of camalexin. Early production of jasmonic acid (JA) 12 h after inoculation with Pst/avrRpt2 was absent in all plants expressing NahG compared to the other mutants tested here. These genetic studies unravel pleiotropic changes in defence signalling of NahG plants that are unlikely to result from their low SA content. This adds unexpected difficulties in the interpretation of earlier findings based solely on NahG plants. 相似文献
989.
A Mak-like kinase is a repressor of GAMYB in barley aleurone 总被引:8,自引:0,他引:8
990.
Freezing induced direct cell injury has been explained by a two-factor hypothesis-intracellular ice formation (IIF) at rapid cooling rates, and solution effects at slow cooling rates. Even though IIF is generally believed to be a major injury mechanism at rapid cooling rates, injury by solution effects is not fully understood and several injury mechanisms have been suggested. Solution effects have generally been considered the result of the elevated electrolyte concentration within the intracellular and extracellular space during freezing. In addition to the injury by this elevated electrolyte concentration, freezing injury associated with eutectic crystallization was investigated. To examine the injury associated with eutectic crystallization, two different experiments were designed and performed. In the first experiment, two groups of AT-1 rat prostate tumor cell suspensions were frozen and thawed on a cryomicroscope in the same way except that eutectic crystallization was initiated in only one group. During the second experiment, AT-1 cells were suspended in several different media, which have different eutectic crystallization temperatures, and exposed to a single cooling-warming cycle with varying end temperature of the protocol on a directional solidification stage. After both experiments, post-thaw viability was evaluated and compared. The post-thaw viability drops significantly upon the occurrence of the eutectic crystallization regardless of suspending media, which suggests direct cell injury associated with eutectic crystallization. Based on these observations, two possible injury mechanisms are anticipated: (i) mechanical damage to the cell membrane due to eutectic crystallization, and (ii) intracellular eutectic formation (IEF). The proposed mechanisms provide a more comprehensive physical explanation of freezing induced cell injury and extend the understanding on solution effects. 相似文献