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31.
Michael Krawczak Birgitte Smith-Sorensen Jrg Schmidtke Vijay V. Kakkar David N. Cooper Eivind Hovig 《Human mutation》1995,5(1):48-57
The spectrum of somatic TP53 single basepair substitutions detected in 955 cancers was compared with that of 2,224 different germline mutations in 279 different human genes (other than TP53), reported as the cause of inherited disease. This comparison reveals that, disregarding a relatively small subset (12%) of TP53 mutations that probably result from the action of exogenous mutagens, both the relative rates and the nearest-neighbor spectra of single basepair substitutions are similar in the two datasets. This spectral resemblance suggests that a substantial proportion of cancer-associated somatic TP53 mutations result from endogenous cellular mechanisms. The likelihood of clinical observation of a particular mutation type differs, however, between tumors and genetic diseases, when the chemical properties of the resulting amino acid substitutions are considered. Together with a sixfold higher observation likelihood for mutations at evolutionary conserved residues, this finding argues that selection is a critical factor in determining which TP53 mutations are found to be associated with human cancer. © 1995 Wiley-Liss, Inc. 相似文献
32.
The control of retinogeniculate transmission in the mammalian lateral geniculate nucleus 总被引:13,自引:0,他引:13
S. M. Sherman C. Koch 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1986,63(1):1-20
Summary In the mammalian visual system, the lateral geniculate nucleus is commonly thought to act merely as a relay for the transmission of visual information from the retina to the visual cortex, a relay without significant elaboration in receptive field properties or signal strength. However, many morphological and electrophysiological observations are at odds with this view. Only 10–20% of the synapses found on geniculate relay neurons are retinal in origin. Roughly half of all synapses derive from cells in layer VI of visual cortex; roughly one third are inhibitory and GABAergic, derived either from interneurons or from cells of the nearby perigeniculate nucleus. Most of the remaining synapses probably derive from cholinergic, noradrenergic, and serotonergic sites within the brainstem reticular formation. Moreover, recent biophysical studies have revealed several ionic currents present in virtually all thalamic neurons. One is a Ca2+-dependent K+ current underlying the afterhyperpolarization (or the IAHP), which may last up to 100–200 ms following an action potential. Activation of the IAHP leads to spike frequency adaptation in response to a sustained, suprathreshold input. Intracellular recordings from other neuronal preparations have shown that the IAHP can be blocked by noradrenalin or acetylcholine, leading to an increased cellular excitability. Another ionic current results from a voltage- and time-dependent Ca2+ conductance that produces a low threshold spike. Activation of this conductance transforms a geniculate neuron from a state of faithful relay of information to one of bursting behavior that bears little relationship to the activity of its retinal afférents. We propose that state-dependent gating of geniculate relay cells, which may represent part of the neuronal substrate involved in certain forms of selective visual attention, can be effected through at least three different mechanisms: (1) conventional GABAergic inhibition, which is largely controlled via brainstem and cortical afferents through interneurons and perigeniculate cells; (2) the IAHP, which is controlled via noradrenergic and cholinergic afferents from the brainstem reticular formation; and (3) the low threshold spike, which may be controlled by GABAergic inputs, cholinergic inputs, and/or the corticogeniculate input, although other possibilities also exist. Furthermore, it seems likely that gating functions involving the corticogeniculate pathway are suited to attentional processes within the visual domain (e.g., saccadic suppression), whereas brain-stem inputs seem more likely to have more global effects that switch attention between sensory systems. In any case, it is now abundantly clear that geniculate circuitry and the intrinsic electrophysiological properties of geniculate neurons are no longer compatible with the notion that the lateral geniculate nucleus serves as a simple relay. 相似文献
33.
A. A. M. Tax J. J. Denier van der Gon C. C. A. M. Gielen C. M. M. van den Tempel 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1989,76(1):55-63
Summary We have compared muscle activation in the control of slow isotonic movements and isometric contractions. Specific attention has been given to the contribution of the two force-grading mechanisms, the recruitment of motor units and the modulation of firing frequency in motor units that have already been recruited. The recruitment order of the m. biceps motor units under study was the same during isometric contractions and slow isotonic movements. However, the recruitment thresholds of the m. biceps units were considerably lower for both isotonic flexion and extension movements, even at velocities as low as 2 deg/s, than for isometric contractions. Furthermore, firing frequency at recruitment was found to depend on the motor task: at recruitment the motoneurone starts firing with a higher firing frequency during isotonic flexion movements and a lower firing frequency during isotonic extension movements than during isometric contractions. Two main conclusions can be drawn from these results. First of all, the concept of one single activation parameter (total synaptic drive?) cannot account for the motor-unit behaviour observed during our experiments: the relative contribution of the two forcegrading mechanisms is different for different tasks. Secondly, the distribution of activity among flexor motoneurone pools is different for isometric contractions and isotonic movements. 相似文献
34.
The modulation of monosynaptic forelimb reflexes by tonic neck positions was investigated in cats with the head fixed.Lateral flexion of the body in a horizontal plane markedly facilitates reflexes of the deep radial nerve (DR) in the ipsilateral forelimb, while the antagonistic ulnar nerve (ULN) reflexes are strongly inhibited. Opposite effects are seen after contralateral body movement.Dorsiflexion of the body clearly increases DR-reflexes and exerts a reciprocal although more pronounced inhibition on ULN reflexes. Opposite effects appear after ventriflexion.The reflex modulation starts with head-body displacements of approximately 5° and increases with increasing angles. Furthermore reflex modulation does not depend on the intact cerebrum and cerebellum. The comparison of forelimb and hindlimb reflexes shows a decrease of the neck influences along the spinal cord.Supported by Sonderforschungsbereich Hirnforschung und Sinnes-physiology (SFB 70) der Deutschen Forschungsgemeinschaft (DFG).Essential parts of this paper will be submitted by A. F. as a thesis to the Faculty of Medicine, Freiburg/Breisgau, Germany. 相似文献
35.
H. W. Pia 《Acta neurochirurgica》1985,77(3-4):81-102
Summary Cerebral plasticity constitutes one of the most decisive factors in recovery and readaptation after cerebral lesions. In contrast to the considerable progress in current studies on normal neuronal plasticity including the idea of l'homme neuronal, the concept of plasticity postulated by Albrecht Bethe in 1929 received little attention. The author, as a neurosurgeon, has tried to describe cranial morphological plasticity, morphological and functional plasticity in infantile encephalopathies and especially in hemiatrophic lesions. It is supposed that a true morphological substrate exists due to compensatory hyperplasia of the uninvolved hemisphere.Modern neurosurgical techniques have demonstrated that the functional plastic capacity is much larger than has been supposed, even in the elderly. Some aspects of the mechanisms of compensation and decompensation of cortical and subcortical structures as well as of the central regulation systems are discussed. The full extent of the amazing recovery and functional reorganization is reached by plastic capacity, personal motivation, adequate training and sufficient time.The contribution ends with an exposition of a personal philosophy concerning psycho-somatic dualism, the body-mind problem, the future of the human brain and the ethical outlook, based on the progressive biological evolution of the basal neocortex and the immanent functional development (H. Spatz).In grateful memory of my paternal friends, the great German brain researchers Julius Hallervorden (1882–1965) and Hugo Spatz (1888–1969). 相似文献
36.
Manish Kuchakulla Manish Narasimman Kajal Khodamoradi Zahra Khosravizadeh Ranjith Ramasamy 《Andrologia》2021,53(1):e13615
Spermatogenesis is the essential process to maintain and promote male fertility. It is extraordinarily complex with many regulatory elements and numerous steps. The process involves several cell types, regulatory molecules, repair mechanisms and epigenetic regulators. Evidence has shown that fertility can be negatively impacted by reduced sperm DNA integrity. Sources of sperm DNA damage include replication errors and causes of DNA fragmentation which include abortive apoptosis, defective maturation and oxidative stress. This review outlines the process of spermatogenesis, spermatogonial regulation and sperm differentiation; additionally, DNA damage and currently studied DNA repair mechanisms in spermatozoon are also covered. 相似文献
37.
38.
The shift from inpatient care to the ambulatory sector is a central aspiration of European health systems. Despite demonstrated benefits, health reforms have struggled to realize their potential. In this context, we discuss recent hospital sector reforms in Switzerland and analyze the content, process, and role of evidence in the recent introduction of policies to substitute inpatient care with ambulatory care. The prevailing payment system incentivized hospitals to provide unnecessary and costly inpatient services, but federal reform on tariff structures was deemed politically unfeasible. Instead, driven by the pressure to contain costs, cantonal and federal health authorities began to deny reimbursement for selected inpatient procedures in 2017. These regulatory measures were effective in reducing inpatient admissions and health care costs. This case study illustrates that clear, simple messages about hospital sector reform can raise awareness of the need for change. However, the evidence used in the policy process was limited and not critically reviewed. Stakeholders used long-standing international comparisons of inpatient substitution potential to legitimize policies, but not to develop them. The analysis restates the importance of inter- and intranational comparative analyses and institutions such as health observatories and suggests aligning health system governance more proactively with international developments. 相似文献
39.
以5%乙酸冲洗正常人膀胱,获得膀胱粘膜酸溶性提取物。电泳凝胶琼脂糖弥散法抗菌实验分析表明,膀胱粘膜酸溶性提取物中有一条主蛋白带(称之为HBP)对致病性大肠杆菌ML-35P株有抗菌活性。以超滤方法对膀胱粘膜酸溶性提取物进行分离纯化,获得分子量低于1×10~4的超滤纯化样品,其中主要含HBP。琼脂糖弥散法抗菌实验结果表明,超滤纯化样品对大肠杆菌ML-35P株、绿脓杆菌ATCC27853株、金黄色葡萄球菌ATCC25923株及血链球菌S_34Sr株均有很强的抗菌活性。采用Tricine-SDS-pAGE鉴定,超滤纯化样品主要显示为两条分子量分别为6.7×10~3和8.5×10~3的多肽。研究结果首次提示,人膀胱粘膜内存在抗菌活性很强的内源性抗生肽,是膀胱抗感染防御的主要因素。 相似文献
40.
Injections of pentobarbital have been shown to produce drinking in both deprived and nondeprived rats and a number of other studies have shown that pentobarbital is a potent renin releasor. Since renin has been shown to be involved in thirst regulatory mechanisms and since the dipsogenic actions of other renin-releasing agents have been blocked by nephrectomy, we sought to determine whether or not pentobarbital-induced drinking relies on a renal dipsogen. Rats were either "sham" operated or nephrectomized under ether anesthesia. Five to six hours later, animals in each group were injected with either 9.5 mg/kg pentobarbital sodium or vehicle, and intakes were measured 60 minutes later. Statistical analysis of water intakes indicated that pentobarbital produced significant drinking in both control operated and in nephrectomized rats, and that the intakes in these two groups did not differ. These results indicate that pentobarbital-induced drinking is not secondary to increased plasma renin activity and may suggest the involvement of central mechanisms in the drinking response. 相似文献