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991.
The potency and specificity of a novel organic I
h
current blocker DK-AH 268 (DK, Boehringer) was studied in cultured rat trigeminal ganglion neurons using whole-cell patch-clamp
recording techniques. In neurons current-clamped at the resting potential, the application of 10 μm DK caused a slight hyperpolarization of the membrane potential and a small increase in the threshold for action potential
discharge without any major change in the shape of the action potential. In voltage-clamped neurons, DK caused a reduction
of a hyperpolarization-activated current. Current subtraction protocols revealed that the time-dependent, hyperpolarization-activated
currents blocked by 10 μm DK or external Cs+ (3 mm) had virtually identical activation properties, suggesting that DK and Cs+ caused blockade of the same current, namely I
h
. The block of I
h
by DK was dose-dependent. At the intermediate and higher concentrations of DK (10 and 100 μm) a decrease in specificity was observed so that time-independent, inwardly rectifying and noninactivating, voltage-gated
outward potassium currents were also reduced by DK but to a much lesser extent than the time-dependent, hyperpolarization-activated
currents. Blockade of the time-dependent, hyperpolarization-activated currents by DK appeared to be use-dependent since it
required hyperpolarization for the effect to take place. Relief of DK block was also aided by membrane hyperpolarization.
Since both the time-dependent current blocked by DK and the Cs+-sensitive time-dependent current behaved as I
h
, we conclude that 10 μm DK can preferentially reduce I
h
without a major effect on other potassium currents. Thus, DK may be a useful agent in the investigation of the function of
I
h
in neurons.
Received: 3 March 1995/Revised: 8 July 1997 相似文献
992.
J. L. Weiner C. F. Valenzuela P. L. Watson †C. J. Frazier †‡T. V. Dunwiddie 《Journal of neurochemistry》1997,68(5):1949-1959
Abstract: The ability of ethanol to enhance GABAA receptor function remains controversial; conflicting observations have been made even in the same brain region, and when using apparently similar methodologies. In this study we characterized a single protocol variable, the initial incubation temperature of brain slices, that had dramatic effects on the ethanol sensitivity of GABAA inhibitory postsynaptic currents (IPSCs) recorded from rat hippocampal CA1 pyramidal neurons. Incubation of hippocampal slices at relatively low temperatures (11–15°C) immediately after slice preparation significantly affected a number of physiological and biochemical parameters. Such slices showed a decrease in extracellular inhibitory postsynaptic potential amplitude, a significant increase in the ethanol sensitivity of GABAA IPSCs in CA1 pyramidal neurons, no change in pentobarbital or flunitrazepam potentiation of IPSCs, and an increase in basal protein kinase C (PKC) activity relative to slices incubated at 31–33°C. In addition, the increase in ethanol sensitivity of GABAA IPSCs was blocked by chelerythrine, a selective inhibitor of PKC. These results suggest that differences in hippocampal slice incubation protocols may have contributed to the disparate results of previous investigations of ethanol modulation of GABAA receptor-mediated synaptic transmission in the rat hippocampus. In addition, these findings provide further evidence that PKC activity positively modulates the interaction between ethanol and GABAA receptors in the mammalian brain. 相似文献
993.
Orlando Necchi Jr 《Phycological Research》1997,45(1):39-45
Microhabitat and plant structure of seven Batrachospermum populations (four of Batrachospermum delicatulum (=Sirodotia delicatula), one of Batrachospermum macrosporum and two of the ‘Chantransia’ stage), including the influence of physical variables (current velocity, depth, irradiance and substratum), were investigated in four streams of São Paulo State, southeastern Brazil. The populations of B. delicatulum and the ‘Chantransia’ stage occurred under very diverse microhabitat conditions, which probably contributes to their wide spatial and seasonal distribution in Brazilian streams. Results suggest branch reconfiguration as a probable mechanism of adaptation to current velocity based on the occurrence of: (i) B. macrosporum (a large mucilaginous form with presumably little ability for branch reconfiguration) under lower current velocity than B. delicatulum; (ii) only dense plants in populations with high current velocities (> 60 cm s?1), whereas 53–77% of dense plants were seen in populations exposed to lower currents (< 40 cm s?1); (iii) positive correlations of plant length with internode length in populations under low current velocities and negative correlation in a population with high velocity (132 cm s?1); and (iv) negative correlations of current velocity with plant diameter and internode length in a population under high flow. This study, involving mainly dioecious populations, revealed that B. delicatulum displayed higher fertilization rates than B. macrosporum. A complementary explanation for a dioecious species to increase fertilization success was proposed consisting of outcrossing among intermingled male and female adjacent plants within an algal spot. 相似文献
994.
995.
Singh Jaipaul Hustler Brenda I. Waring John J. Howarth Frank C. 《Molecular and cellular biochemistry》1997,176(1-2):127-134
This study employs both dietary and physiological studies to investigate the relationship between calcium (Ca2+) and magnesium (Mg2+) signalling in the mammalian myocardium. Rats maintained on a low Mg2+ diet (LMD; 39 mg Kg-1 Mg2+ in food) consumed less food and grew more slowly than control rats fed on a control Mg2+ diet (CMD; 500 mg Kg-1 Mg2+ in food). The Mg2+ contents of the heart and plasma were 85 ± 3% and 34 ± 6.5%, respectively relative to the control group. In contrast, Ca2+ contents in the heart and plasma were 177 ± 5% and 95 ± 3%. The levels of potassium (K+) was raised in the plasma (129 ± 16%) and slightly decreased in the heart (88 ± 6%) compared to CMD. Similarly, sodium (Na+) contents were slightly higher in the heart and lowered in the plasma of low Mg2+ diet rats compared to control Mg2+ diet rat. Perfusion of the isolated Langendorff's rat heart with a physiological salt solution containing low concentrations (0-0.6 mM) of extracellular magnesium [Mg2+]0 resulted in a small transient increase in the amplitude of contraction compared to control [Mg2+]0 (1.2 mM). In contrast, elevated [Mg2+]0 (2-7.2 mM) caused a marked and progressive decrease in contractile force compared to control. In isolated ventricular myocytes the L-type Ca2+ current (ICa,L was significantly (p < 0.001) attenuated in cells dialysed with 7.1 mM Mg2+ compared to cells dialysed with 2.9 µM Mg2+. The results indicate that hypomagnesemia is associated with decrease levels of Mg2+ and elevated levels of Ca2+ in the heart and moreover, internal Mg2+ is able to modulate the Ca2+ current through the L-type Ca2+ channel which in turn may be involved with the regulation of contractile force in the heart. 相似文献
996.
Shu CH Yang WK Shih YL Kuo ML Huang TS 《Apoptosis : an international journal on programmed cell death》1997,2(5):463-470
Paclitaxel is a potential anti-cancer agent for several malignancies including ovary, breast, and head and neck cancers. This
study investigated the kinetics of paclitaxel-induced cell cycle perturbation in two human nasopharyngeal carcinoma (NPC)
cell lines, NPC-TW01 and NPC-TW04. NPC cells treated with higher concentrations (0.1 or 1 μM) of paclitaxel showed obvious
G2/M arrest and then converted to a cell population with reduced DNA content, which was detected as a sub-G2 peak in the flow
cytometric histographs. If a low concentration (5 nM) of paclitaxel was used instead, transient G2/M arrest was observed in
NPC cells, which subsequently converted to a sub-G1 form during the treatment period. Internucleosomal fragmentation and chromatin
condensation were detectable in these sub-G1 and sub-G2 cells, suggesting that persistent or transient G2/M arrest is a prerequisite
step for apoptosis elicited by varying doses of paclitaxel. The levels of cyclins A, B1, D1, E, CDK 1 (CDC 2), CDK 2 and proliferating
cell nuclear antigen (PCNA) were unchanged in NPC cells following treatment with any concentration of paclitaxel; however,
apoptosis-related cyclin B1-associated CDC 2 kinase was highly activated by paclitaxel even at concentrations as low as 5
nM, which is consistent with the finding that low-dose paclitaxel is also able to induce apoptosis in NPC cells. Activation
of cyclin B1-associated CDC 2 kinase seems to be an important G2/M event required for paclitaxel-induced apoptosis, and this
activation of cyclin B1/CDC 2 kinase could be attributed to the increased activity of CDK 7 kinase.
This revised version was published online in November 2006 with corrections to the Cover Date. 相似文献
997.
Sequence analysis of lacZ~- mutations induced by ion beam irradiation in double-stranded M13mp18DNA 总被引:4,自引:0,他引:4
While M13mpl8 double-stranded DNA was irradiated with ion beam, and transfected into E. coli JM103, a decrease of transfecting activity was discovered. The lacZ-mutation frequency at 20% survival could reach (3.6-16.8) × 104, about 2.3-10 times that of unirradiated M13DNA. Altogether, 27 lacZ~ mutants were select-ed, 10 of which were used for sequencing. 7 of the sequenced mutants show base changes in 250-bp region examined (the remaining 3 mutants probably have base changes outside the regions sequenced). 5 of the base-changed mutants contain more than one mutational base sites (some of them even have 5-6 mutational base sites in 250-bp region ex-amined) ; this dense distribution of base changes in polysites has seldom been seen in X-rays, γ-rays or UV induced DNA mutations. Our experiments also showed that the types of base changes include transitions( 50 % ), transversions (45% ) and deletion (5% ); no addition or duplication was observed. The transitions were mainly C→T and A→G; the transversion 相似文献
998.
The experiments were perfomed on transvcrsus abdominis muscle of Elaphe dione by subendothelial recording. The results indicate that in snake motor nerve endings there exist four types of K* channels, i.e. voltage-dependent fast and slow K channels, Ca2 -activated K channel and ATP-sensitive K channel, (i) The typical wave form of snake terminal current was the double-peaked negativity in standard solution. The first peak was at-tributed to Na influx (INa) in nodes of Ranvier. The second one was blocked by 3, 4-aminopyridine (3, 4-DAP) or te-traethylammonium (TEA), which corresponded to fast K outward current (IKF) through the fast K* channels in terminal part, (ii) After IKF as well as the slow K current (IKS) were blocked by 3, 4-DAP, the TEA-sensitive Ca2 -dependent K current (IK(Ca)) passing through Ca2 -activated K channel was revealed, whose amplitude depended on [K ]and [Ca2 ] It was blocked by Ba2 , Cd2 or Co2 . (iii) IK.F and IK(Ca) were blocked by TEA, while IK.S was retained. It 相似文献
999.
Šimurda Jiří Šimurdová Milena Bravený Pavel Christé Georges 《Molecular and cellular biochemistry》1996,160(1):5-12
A quantitative model of Ca-turnover in cardiac cells that incorporates negative feedback modulation of sarcolemmal calcium transport (via Ca channels and Na/Ca exchange) has been designed. The Na/Ca exchange current was expressed as INaCa = I
NaCar
+
Naca
. The component I
NaCar
reflects slow changes of Ca2+ and Na+ concentrations and depends on the Na/K pump. I
NaCa
is the fast component related to the Ca2+ transient. The single input to the model is an arbitrary sequence of intervals between excitations; outputs are sequences of calcium amounts transferred among the compartments during individual intervals. The model operates with a combination of discrete variables (amounts of Ca transferred during contraction, relaxation and rest) and continuous variables — slow changes in ionic concentrations. Since the model is not formalistic but respects the nature of the underlying elements of the system, it enables us to simulate the known effects of cardiotropic drugs or to predict their unknown mechanisms by visualizing the changes in individual Ca compartments. By altering the parameters, the model also simulates the known species and tissue differences in rate-dependent phenomena. 相似文献
1000.
Ross C. Hoffman Franklin J. Moy Virginia Price Jane Richardson Dennis Kaubisch Eric A. Frieden Jonathan D. Krakover Beverly J. Castner Julie King Carl J. March Robert Powers 《Journal of biomolecular NMR》1996,7(4):273-282
Summary Oncostatin M (OM) is a cytokine that shares a structural and functional relationship with interleukin-6, leukemia inhibitory factor, and granulocyte-colony stimulating factor, which regulate the proliferation and differentiation of a variety of cell types. A mutant version of human OM in which two N-linked glycosylation sites and an unpaired cysteine have been mutated to alanine (N76A/C81A/N193A) has been expressed and shown to be active. The triple mutant has been doubly isotope-labeled with 13C and 15N in order to utilize heteronuclear multidimensional NMR techniques for structure determination. Approximately 90% of the backbone resonances were assigned from a combination of triple-resonance data (HNCA, HNCO, CBCACONH, HBHACONH, HNHA and HCACO), intraresidue and sequential NOEs (3D 15N-NOESY-HMQC and 13C-HSQC-NOESY) and side-chain information obtained from the CCONH and HCCONH experiments. Preliminary analysis of the NOE pattern in the 15N-NOESY-HMQC spectrum and the 13C secondary chemical shifts predicts a secondary structure for OM consisting of four -helices with three intervening helical regions, consistent with the four-helix-bundle motif found for this cytokine family. As a 203-residue protein with a molecular weight of 24 kDa, Oncostatin M is the largest -helical protein yet assigned.To whom correspondence should be addressed. 相似文献