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21.
R. Lemmens-Gruber H. Marei P. Heistracher 《Naunyn-Schmiedeberg's archives of pharmacology》1997,355(2):230-238
GE 68 ((Rac.)-1-[3-(Phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol hydrochloride) is structurally related to propafenone,
and exerts negative inotropic and negative chronotropic effects similar to the parent drug, but lacks any β-adrenoceptor blocking
activity contrary to propafenone. Thus, the electrophysiological effects of GE 68 were studied in papillary muscles, left
atria, Purkinje fibres, sinoatrial nodes and ventricular myocytes of the guinea-pig heart with the intracellular microelectrode
technique and the patch-clamp technique in the cell-attached mode.
The decrease of the maximum upstroke velocity (V˙max) by GE 68 (1 to 10 μM) was use- and frequency-dependent. V˙max recovered from the use-dependent block with a time constant of 4.1 ± 0.6 s. In papillary muscles and Purkinje fibres action
potential duration was shortened, while it was prolonged in left atria and sinoatrial nodes. Half-maximal steady-state inactivation
of the sodium channels was shifted to more negative membrane potentials (control: –91.5 ± 0.8 mV, 10 μM GE 68: –97.9 ± 2.5 mV).
The peak of the current-voltage relationship and the reversal potential were not changed by GE 68. The amplitude of the unitary
current remained unaltered, while open state probability was decreased. The most striking effect of GE 68 was an increase
of the number of sweeps without single channel openings (1 μM: 2 fold, 10 μM: 6 fold). GE 68 also caused a decrease of the
mean open times, and an increase of the mean closed times in unmodified and pronase-modified sodium channels.
Besides the lack of β-adrenoceptor blocking activity, data present a faster recovery from the use-dependent block by GE 68
and a lower affinity to inactivated sodium channels compared to the reference drug propafenone, as well as differences in
the effect on single channel kinetics.
Received: 25 July 1996 / Accepted: 14 October 1996 相似文献
22.
常规PID控制具有结构简单、稳定性好、可靠性高等优点,在调速系统中被广泛应用。但常规PID控制的设计需依靠数学模型,负载、模型参数的变化及非线性因素等影响常规PID的精确调节。单神经元PSD控制器利用神经元的自学习、自组织能力,根据被控对象的变化情况对控制器的权值进行在线调整,达到在线调整PID参数的目的,并且采用无需对象模型的控制算法构成了自适应控制。与常规的PID调节器相比,具有更好的鲁棒性。同时,通过对PSD控制器的改进,在直流伺服系统的仿真应用中得到了较理想的结果。 相似文献
23.
The effects of KB-2796, 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine-2HCl, on the low- and high-voltage activated Ca2+ currents (LVA and HVA ICa, respectively) and on oxidative metabolism were studied in neurons freshly dissociated from rat brain. KB-2796 reduced the peak amplitude of LVA ICa in a concentration-dependent manner with a threshold concentration of 10−7 M when the LVA ICa was elicited every 30 s in the external solution with 10 mM Ca2+. The concentration for half-maximum inhibition (IC50) was 1.9 × 10−6M. At 10−5 M or more of KB-2796, a complete suppression of the LVA ICa was observed in the majority of neurons tested. There was no apparent effect on the current-voltage (I-V) relationship and the current kinetics. KB-2796 delayed the reactivation and enhanced the inactivation of the Ca2+ channel for LVA ICa voltage- and time-dependently, suggesting that KB-2796 preferentially binds to the inactivated Ca2+ channel. KB-2796 at a concentration of3.0 × 10−6M also decreased the peak amplitude of the HVA ICa without shifting the I-V relationship. In addition, KB-2796 reduced the oxidative metabolism (the formation of reactive oxygen species) of the neuron in a concentration-dependent manner with a threshold concentration of3 × 10−6M. It is suggested that the inhibitory action of KB-2796 on the neuronal Ca2+ influx and the oxidative metabolism, in combination with a cerebral vasodilatory action, may reduce ischemic brain damage. 相似文献
24.
The firing rate of locus coeruleus (LC) neurons in rat brain slices was increased reversibly by agents that either elevate intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) or mimic its actions (e.g., forskolin, and activator of adenylate cyclase, 8-Br-cAMP, a membrane permeable analog of cAMP, and Ro20-1724, a preferential inhibitor of cAMP-phosphodiesterase). Intracellular recordings showed that 8-Br-cAMP and forskolin induce a depolarization of LC neurons, accompanied by a decrease in input resistance. The 8-Br-cAMP- and forskolin-elicited depolarization persisted in the presence of cobalt, a calcium channel blocker. Steady-state current-voltage curves revealed that in the voltage range of -50 to -120 mV, 8-Br-cAMP and forskolin induced an inward current, which did not reverse at the potassium equilibrium potential and could not be blocked by tetrodotoxin. Partial replacement of sodium with Tris or choline markedly reduced the depolarization elicited by 8-Br-cAMP. We conclude that 8-Br-cAMP and forskolin act through a common mechanism to increase the firing rate of locus coeruleus neurons by inducing a cAMP-activated inward current, carried out at least in part by sodium ions. 相似文献
25.
本文将聚乙二醇(PEG)比浊法和固相酶联免疫法(ELISA)结合,建立了—较灵敏的免疫复合物(IC)直接固相吸附抗原特异性检测法。利用牛清蛋白(BSA)为已知抗原组份的IC模型,分别对IC直接固相吸附的条件和影响因素、方法的灵敏度、重复性等进行了研究。结果发现IC在解离状态下直接固相吸附后的抗原特异性检测灵敏度明显高于未解离者。该法具有简单易行,灵敏度较高、适于临床测定大量血清样品等优点。 相似文献
26.
F. Tribut B. Lapied A. Duval M. Pelhate 《Pflügers Archiv : European journal of physiology》1991,419(6):665-667
Short-term culture of isolated adult dorsal unpaired median (DUM) neurons of the cockroach Periplaneta americana has been used to study the evolution of the sodium current during the time in culture after axotomy and deafferentation treatment. An increase in the maximum peak amplitude of the sodium current recorded under voltage-clamp conditions with the patch-clamp technique in the whole-cell recording configuration, was only observed between 24h and 72h (75%) without any modification of the kinetics and the voltage-dependence of the current. A decrease in the level of foetal calf serum in the culture medium reduces the amplitude of the sodium current on all days but does not affect its time-course of development which was on the contrary completely abolished by both protein synthesis inhibitors, actinomycin D and cycloheximide. The results obtained in these neurons strongly suggest that a neosynthesis of sodium channel proteins is involved in the evolution of the sodium current induced by axotomy and deafferentation. 相似文献
27.
中国急性心肌梗塞的疾病经济负担 总被引:8,自引:1,他引:7
主要通过对急性心肌梗塞疾病经济负担的研究,总体描述进行二线预防的重要性。资料主要来源于中文文献检索、政府统计报表。主要利用直接医疗费用来计算疾病经济负担,而未考虑直接非医疗费用和间接费用。中日急性心肌梗塞的发病率约为45/10万。55/10万。城市高于农村,男性高于女性。在2000年,急性心肌梗塞的死亡率在城市为32.39/10万,农村为17.99/10万,其死亡率随年龄增长而相应增长。与发病率一样,城市高于农村,男性高于女性。25岁以上人群因急性心肌梗塞而损失的DALY在2000年为3.57DALYs/千人口。怎性心肌梗塞的直接医疗费用在国家卫生部部属医院为28257元/例,省级医院为8663元/例,县级医院为5447无/例。测算2000年急性心肌梗塞的疾病经济负担为13亿元。19亿元。但由于只有10.6%的急性心肌梗塞病人得到临床床治疗,因此,本测算结果可能低估了在中国实际发生的疾病经济负担。 相似文献
28.
J T Fujii 《The Journal of comparative neurology》1992,316(3):279-286
The avian Edinger Westphal nucleus, through the ciliary ganglion, controls accommodation, iris constriction, and blood flow through the choroid. In live brainstem slices, the nucleus is easily identifiable as an olive-shaped cluster of neurons dorsal to the oculomotor nerve and nucleus. Intracellular recordings from neurons in the nucleus identified two classes of responses to sustained (300 to 500 ms) injections of depolarizing current. One set of cells fired action potentials for the duration of the pulse while a second set of cells fired action potentials only transiently, during the first 50 to 100 ms, after which they remained silent regardless of the size of the depolarization. Intracellular recordings followed by injections of the fluorescent dye lucifer yellow revealed that repetitively firing cells were located in the lateral half of the nucleus while non-repetitively or transiently firing cells were located in the medial half. These locations correspond to different Edinger Westphal subdivisions which have distinct inputs and target populations. The varying firing patterns are discussed with reference to the known functions of the subdivisions in which they occur. Replacement of calcium by magnesium in the extracellular medium had no effect on the number of action potentials fired by non-repetitively firing cells, suggesting that a calcium-activated potassium current is not responsible for suppressing repetitive firing in these cells. In contrast, in repetitively firing cells removal of extracellular calcium increased the frequency of action potential discharge and decreased the amplitude of afterhyperpolarizations following single action potentials. Addition of cadmium to the bath medium had similar effects.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
29.
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