全文获取类型
收费全文 | 607篇 |
免费 | 41篇 |
出版年
2021年 | 8篇 |
2020年 | 4篇 |
2019年 | 8篇 |
2018年 | 12篇 |
2017年 | 8篇 |
2016年 | 16篇 |
2015年 | 27篇 |
2014年 | 20篇 |
2013年 | 33篇 |
2012年 | 51篇 |
2011年 | 43篇 |
2010年 | 23篇 |
2009年 | 21篇 |
2008年 | 25篇 |
2007年 | 29篇 |
2006年 | 25篇 |
2005年 | 31篇 |
2004年 | 19篇 |
2003年 | 17篇 |
2002年 | 24篇 |
2001年 | 10篇 |
2000年 | 15篇 |
1999年 | 15篇 |
1998年 | 10篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1995年 | 6篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 11篇 |
1991年 | 12篇 |
1990年 | 10篇 |
1989年 | 12篇 |
1988年 | 6篇 |
1987年 | 6篇 |
1986年 | 7篇 |
1985年 | 3篇 |
1984年 | 6篇 |
1983年 | 6篇 |
1981年 | 4篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1973年 | 4篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1968年 | 3篇 |
1967年 | 3篇 |
1918年 | 4篇 |
1916年 | 5篇 |
1915年 | 2篇 |
排序方式: 共有648条查询结果,搜索用时 113 毫秒
1.
Christopher A. Fraker Camillo Ricordi Luca Inverardi Juan Domínguez‐Bendala 《Biology of the cell / under the auspices of the European Cell Biology Organization》2009,101(8):431-440
Beyond its role as an electron acceptor in aerobic respiration, oxygen is also a key effector of many developmental events. The oxygen‐sensing machinery and the very fabric of cell identity and function have been shown to be deeply intertwined. Here we take a first look at how oxygen might lie at the crossroads of at least two of the major molecular pathways that shape pancreatic development. Based on recent evidence and a thorough review of the literature, we present a theoretical model whereby evolving oxygen tensions might choreograph to a large extent the sequence of molecular events resulting in the development of the organ. In particular, we propose that lower oxygenation prior to the expansion of the vasculature may favour HIF (hypoxia inducible factor)‐mediated activation of Notch and repression of Wnt/β‐catenin signalling, limiting endocrine cell differentiation. With the development of vasculature and improved oxygen delivery to the developing organ, HIF‐mediated support for Notch signalling may decline while the β‐catenin‐directed Wnt signalling is favoured, which would support endocrine cell differentiation and perhaps exocrine cell proliferation/differentiation. 相似文献
2.
The hydroosmotic responses induced by oxytocin and 8-bromo-cyclic AMP, in frog and toad urinary bladders, were recorded minute by minute. 3HHO and 45Ca unidirectional fluxes as well as prostaglandin B2 liberation were also measured. It was observed that: (1) Addition of the calcium ionophore A23187 or quinidine to the serosal bath inhibited the response to oxytocin, but not to 8-bromo-cyclic AMP, while increasing prostaglandin E1 liberation into the serosal but not into the mucosal bath. (2) Addition of A23187 to the mucosal bath induced a transient and temperature-dependent inhibition of the response elicited by 8-bromo-cyclic AMP. The time-course of this reduction in water permeability and its sensitivity to medium temperature were similar to those observed after the withdrawal of agonist, but clearly different of those observed after intracellular acidification. (3) The hydroosmotic response was also transitorily inhibited when the Ca2+ concentration was step-changed in the mucosal bath. (4) When added to the mucosal or to the serosal baths, the ionophore increased either the apical or the laterobasal Ca2+ permeabilities. It is concluded that manipulation of intracellular Ca2+ interferes with the hydroosmotic response at two different levels. (1) A first target point located 'pre-cyclic-AMP production'. This effect would be mediated by prostaglandin liberation. (2) A second target point located after cyclic AMP production and before the 'temperature-dependent rate-limiting step'. This effect is probably related to the mechanism controlling the insertion and removal of water channels. 相似文献
3.
I. Dore E. L. Dekker C. Porta M. H. V. Van Regenmortel 《Journal of Phytopathology》1987,120(4):317-326
Five monoclonal antibodies (McAbs) were raised to the tobamovirus, odontoglossum ringspot virus (ORSV). All five McAbs reacted with the virus in double antibody sandwich (DAS) ELISA but not in an ELISA using virus-coated plates. All the McAbs recognized a panel of ORSV strains and isolates, although one of the antibodies reacted better with some isolates and another reacted less with certain isolates than with type ORSV. It was possible to use the same McAbs both as coating and as biotinylated antibody in DAS-ELISA. None of the five McAbs was able to bind to orchid strains of tobacco mosaic virus (TMV). In order to detect strains of both viruses, ORSV and TMV, in infected orchids it was necessary to include also McAbs raised against TMV in the immunoassays. The use of a mixed polyclonal-monoclonal antibody DAS-ELISA system is advocated for detecting both tobamoviruses in orchids. 相似文献
4.
Luigi D. Notarangelo Ornella Parolini Fulvio Porta Franco Locatelli Arnalda Lanfranchi Massimo Marconi Luigi Nespoli Alberto Albertini Ian W. Craig Alberto G. Ugazio 《Human genetics》1991,88(2):237-241
Summary We report on a thrombocytopenic female belonging to a pedigree with the Wiskott-Aldrich syndrome (WAS). Restriction fragment length polymorphism (RFLP) analysis with probe M27, closely linked to the WAS gene, demonstrated that she is a carrier of WAS. Both small-sized and normal-sized platelets were present, suggesting that, unlike the vast majority of WAS carriers, she does not manifest nonrandom X-chromosome inactivation in the thrombopoietic cell lineage. Study of X-chromosome inactivation by means of RFLP and methylation analysis demonstrated that the pattern of X-chromosome inactivation was nonrandom in T lymphocytes, but random in granulocytes. While this is the first complete report on the occurrence of thrombocytopenia in a carrier female of WAS as the result of atypical lyonization, it also suggests that expression of the WAS gene occurs at (or extends up to) a later stage than the multipotent stem cell along the hematopoietic differentiation pathway. 相似文献
5.
Substance P as a transglutaminase substrate: identification of the reaction products by fast atom bombardment mass spectrometry 总被引:1,自引:0,他引:1
R Porta C Esposito S Metafora P Pucci A Malorni G Marino 《Analytical biochemistry》1988,172(2):499-503
Substance P was found to be an effective acyl donor substrate of transglutaminase in vitro, the reaction products having been examined by both sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fast atom bombardment mass spectrometry. Electrophoretic experiments showed that Substance P incorporated 14C-labeled polyamines when incubated with purified guinea pig liver transglutaminase and Ca2+. Extensive use of fast atom bombardment mass spectrometry allowed to establish that: i) a 1:1 adduct Substance P-spermine is formed; ii) only a single glutamine residue out of two, i.e. Gln-5, acts as acyl donor, iii) the single lysine residue of the neuropeptide is unable to act as acyl acceptor. A direct analytical methodology to detect transglutaminase reaction products is described. 相似文献
6.
Inhibition of adenylate cyclase by transglutaminase-catalyzed reactions in pigeon erythrocyte ghosts
R Porta A De Santis C Esposito G F Draetta A Di Donato G Illiano 《Biochemical and biophysical research communications》1986,138(2):596-603
We report the occurrence in pigeon erythrocytes of a soluble Ca2+-dependent transglutaminase (TGase) activity. The effect of the erythrocyte ghost protein modifications, determined by TGase-catalyzed reactions, on adenylate cyclase, phospholipid methyltransferase I and II activities and on the lipidic matrix fluidity of the membrane was investigated by using a purified guinea pig liver TGase preparation. The results showed a significant inhibitory effect of such modifications both on the basal and on the variously stimulated (by NaF, Gpp(NH)p alone or in the presence of 1-isoproterenol) adenylate cyclase activity. By contrast, both the phospholipid methylation and the fluidity of the lipidic matrix of the membrane were unaffected by TGase-mediated reactions. These data suggest a new possible inhibitory mechanism of the cyclic AMP synthesis which might be triggered by the enhancement of the cytosolic Ca2+ concentration. 相似文献
7.
Ada Manzocchi Pierantonio Biondi Camillo Secch Enzo Santaniello 《Journal of neurochemistry》1986,46(6):1895-1898
The methyl ester of succinic semialdehyde (SSA) was examined as a substrate for succinate semialdehyde dehydrogenase (SSADH) from rat brain. It was found that the ester can be oxidized by the enzyme. Values of Km for SSA-Me were higher than for those for SSA, and for this substrate the enzyme showed a substrate-dependent inhibition. This finding suggests that the carboxylate group of SSA is not essential in the process of inhibition of SSADH by the substrate. Cyclopropyl analogues of SSA, cis- and trans-1-formyl-cyclopropan-2-carboxylic acids, were also individually tested as substrates of SSADH. Only the trans isomer was found to be oxidized to the corresponding dicarboxylic acid; it inhibited the enzyme in the same range of concentrations as SSA. The above data suggest that, as for gamma-aminobutyric acid, SSA is present in an unfolded, transoid conformation at the active site of SSADH. 相似文献
8.
Camillo Peracchia 《The Journal of membrane biology》1984,81(1):49-58
Summary This paper reports the inhibitory effects of calmidazolium (CDZ), a calmodulin inhibitor, on electrical uncoupling by CO2. Membrane potential and coupling ratio (V
2/V1) are measured in two neighboring cells ofXenopus embryos (16 to 64 cell stage) for periods as long as 5.5 hr. Upon exposure to 100% CO2, control cells consistently uncouple even if the CO2 treatments are repeated every 15 min for 2.5 hr. CDZ (5×10–8–1×10–7
m) strongly inhibits uncoupling. The inhibition starts after 30, 50 and 60 min of treatment with 1×10–7, 7×10–8 and 5×10–8
m CDZ, respectively, is concentration-dependent and partially reversible. In the absence of CO2, CDZ also improves electrical coupling. CDZ has no significant effect on membrane potential and nonjunctional membrane resistance. These data suggest that calmodulin or a calmodulin-like protein participates in the uncoupling mechanism. 相似文献
9.
Camillo Peracchia 《The Journal of membrane biology》1990,117(1):79-89
Summary Electrical uncoupling of crayfish septate axons with acidification has been shown to cause a substantial increase in [Ca2+]i which closely matches in percent the increase in junctional resistance. To determine the origin of [Ca2+]i increase, septate axons have been exposed either to drugs that influence Ca2+ release from internal stores, caffeine and ryanodine, or to treatments that affect Ca2+ entry. A large increase in junctional resistance and [Ca2+]i maxima above controls resulted from addition of caffeine (10–30mm) to acetate solutions, while a substantial decrease in both parameters was observed when exposure to acetate-caffeine was preceded by caffeine pretreatment. In contrast, ryanodine (1–10 m) always caused a significant decrease in junctional resistance and [Ca2+]i maxima when applied either together with acetate or both before and with acetate. Calcium channel blockers such as La3+, Cd2+ and nisoldipine had no effect, while an increase in the [Ca2+] of acetate solutions either decreased junctional resistance and [Ca2+]i maxima or had no effect. The data suggest that cytoplasmic acidification causes an increase in [Ca2+]i by releasing Ca2+ from caffeine and ryanodine-sensitive Ca2+ stores. The increase in [Ca2+]i results in a decrease in gap junction conductance. 相似文献
10.
Hydrochlorothiazide (HCTZ) was shown to inhibit the transepithelial NaCl transport and the apical Na+-Cl? symport and to depolarize the apical membrane potential in the rabbit gallbladder epithelium. The depolarization was likely related to the opening of a Cl? conductance. To better understand whether an apical Cl? leak is involved in the mechanism of action of HCTZ, the transapical Cl? backflux was measured radiochemically by the washout technique. The gallbladder wall, pretreated with pronase on the serosal side to homogenize the subepithelium, was loaded with 36Cl? on the luminal side; mucosal and serosal 36Cl? effluxes (J m , J s ) were then measured every 2 min. The pretreatment with pronase did not alter the membrane potentials and the selectivity of the epithelium. Under control conditions and the tissue in steady-state, J m and J s time courses were each described by two exponential decays (A,B); the rate constants, k A and k B , were 0.71 ±0.03 and 0.16±0.01 min?1, respectively, and correspondingly the half-times (t 1 2A , t 1 2B ) were 1.01±0.05 and 5.00±0.44 min (n=10); these parameters were not significantly different for J m and J s time courses. J s was always greater than J m (J s /J m =2.02±0.22 and 1.43 ±0.17 for A and B decays). Under SCN? treatment in steady-state conditions, both J m and J s time courses were described by only one exponential decay, the component B being abolished. Moreover t 1 2A was similar to that predictable for the subepithelium. It follows that it is the component B which exits the epithelial compartment. Based on the intracellular specific activity and 36Cl? J m B at 0 min time of the washout experiment, the cell-lumen Cl? backflux in steady-state was calculated to be equal to about 2 μmol cm?2hr?1, in agreement with the value indirectly computable by other techniques. The experimental model was well responsive to different external challenges (increases in media osmolalities; luminal treatment with nystatin). HCTZ (2.5 · 10?4 m) largely increased 36Cl? J m B . The increase was abolished by luminal treatment with 10?4 m SITS, which not only brought back the efflux time courses to the ones observed under control conditions but even increased J s /J m of the cellular component, an indication of a reduced J m B . It is concluded that HCTZ opens an apical, SITS-sensitive Cl? leak, which contributes to dissipate the intracellular Cl? accumulation and to inhibit the NaCl transepithelial transport. Moreover, the drug is likely to reduce the basal electroneutral Cl? backflux supported by Na+-Cl? cotransport, in agreement with the inhibition of the cotransport itself. 相似文献