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61.
鉴于热休克蛋白90β(hsp90β)基因内含子中含有维生素D3受体(VDR)结合位点,为探讨作为核受体家族成员的VDR是否对核受体特异分子伴侣的hsp90β基因的表达具有调控作用,我们开展了本项研究。分别将野生型VDR、含N端(1~133氨基酸残基)及C端(281~427氨基酸残基)片段的VDR突变体真核表达质粒与人hsp90β基因调控片段(-1039/+1531)介导的氯霉素乙酰基转移酶(CAT)报告基因质粒共转染Jurkat细胞,检测正常及经热休克(42℃,1h)处理后细胞裂解液中CAT活性。结果表明VDRN端增强、而C端抑制hsp90β的组成性表达;在热诱导条件下野生型VDR对hsp90β的表达有一定的抑制作用,而其C端片段的抑制较强。为进一步研究VDR对细胞内源性热休克基因表达的影响,我们用RTPCR方法研究了VDR的对细胞内hsp90β基因mRNA水平的影响,发现VDR过表达对hsp90β的热诱导表达明显抑制。结果提示VDR对hsp90β基因的组成性和热诱导表达的调控机制不同。 相似文献
62.
C. Köhler A. Persson T. Melander E. Theodorsson G. Sedvall T. Hökfelt 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1989,75(2):375-380
Summary Using X-ray film autoradiography the distribution of 125I-galanin binding sites was studied in the forebrain of monkey and man. In the monkey a high density was found in all areas of the neocortex, especially layer 4, and in certain subfields in the hippocampal region. Also in the human brain high activity was seen in neocortex, mainly layer 6 and in hippocampal areas, as well as in amygdala, piriform cortex and hypothalamus. These results suggest that the 29-amino acid peptide galanin may be involved in the regulation of higher cortical functions in primates. 相似文献
63.
The central role of interleukin-1 (IL-1) in several disease processes, including fever and inflammation, makes the characterization of ligand-receptor interaction of prime importance.The role of arginine (Arg) side chains of hr-IL-1 in receptor recognition was studied by the modification of Arg residues with the specific reagent 1,2-cyclohexanedione. It was found that chemical modification of Arg residues decreased the binding potential of IL-1 to type I receptor dramatically (by 230-fold) while the affinity to type II receptor was reduced only moderately (by 10-fold), with an insignificant reduction of the dissociation rate.These studies suggest that intact Arg side chains of IL-1 may be necessary for high affinity binding to type I IL-1 receptor, but have less importance for the interaction of IL-1 with type II IL-1 receptor.This observation may be useful in the study of type II IL-1 receptor-mediated biological responses and design of receptor-subtype specific ligands as well. 相似文献
64.
Luo Ling Xu Daniel W. McVicar Adit Ben-Baruch Douglas B. Kuhns James Johnston Joost J. Oppenheim Ji Ming Wang 《European journal of immunology》1995,25(9):2612-2617
The diversity of monocyte chemotactic protein (MCP)3 target cell types, as well as the capacity of MCP3 to desensitize leukocyte responses to other CC chemokines, suggested that MCP3 may interact with multiple CC chemokine receptors. The purpose of this study is to establish how MCP3 binds and activates monocytes and neutrophils. We show that human monocytes exhibit high-affinity binding for 125I-MCP3 with an estimated Kd of 1–3 nM and about 10000 binding sites/cell. The binding of 125I-MCP3 to monocytes was progressively less well competed by CC chemokines macrophage inflammatory protein (MIP)lα (Kd = 5–10 nM), RANTES (Kd = 5–10 nM), MCP1 (monocyte chemoattractant and activating factor, or MCAF) (Kd = 60 nM) and MIP1β (Kd > 100 nM). On the other hand, unlabeled MCP3 displaced the binding of radiolabeled MIP1α, RANTES, MCP1 and MIP1β as effectively as the isologous CC chemokines. In agreement with the binding data, pretreatment of monocytes with MCP3 completely desensitized the calcium flux in response to MIP1α and RANTES. However, MIP1α and RANTES failed to desensitize the response of monocytes to MCP3. MCP3 and MCP1 partially desensitized each other's effects on monocytes. These binding and cross-desensitization results suggest that MCP3 binds and signals through other binding sites in addition to those shared with MIP1α, RANTES and MCP1. The unidirectional competition for MIP1β binding and signaling by MCP3 suggests the existence of an as-yet unidentified site for MCP3 shared with MIP1β. The existence of another unique binding site(s) for MCP3 was further shown by the failure of any of the other CC chemokines to compete effectively for MCP3 binding on neutrophils. MCP3 in our study was also the only human CC chemokine that consistently chemoattracted neutrophils. These results suggest that MCP3 is a ligand that can bind and activate a broad range of target cells through receptors shared by other CC chemokines as well as its own receptor. 相似文献
65.
慢性肾小球肾炎病人白细胞糖皮质激素受体的变化 总被引:1,自引:0,他引:1
以氚标记的地塞米松(~3H-Dex)为配体,用一点分析法测定了23例慢性肾小球肾炎病人混合白细胞的糖皮质激素受体(GCR),平均为8825±2429位点/细胞((?)±SD)。与正常人5154±1635位点/细胞相比相差十分显著,P<0.01。其中16例并发尿毒症患者的GCR平均为9464±2571位点/细胞((?)±SD)。对这种变化的可能机制和临床意义进行了讨论。 相似文献
66.
Origin of impulse initiation in the slowly adapting stretch receptor of the crayfish 总被引:1,自引:0,他引:1
Summary Characteristic for the crayfish stretch receptor is a gradual decrease in axon diameter up to a stretch of axon about 350 m away from the soma-axon border. In response to depolarizing currents applied at different positions along the axon this stretch of axon can be localized as the most excitable membrane region. When depolarizing current steps of 10–25 nA intensity are injected into the soma the first impulse is always triggered in the soma (due to sudden rise in the membrane potential) while the second impulse originates at the axon region of highest escitability. As the intensity of the stimulus is increased the site of impulse initiation along the axon shifts nearer to the receptor soma. At a stimulus intensity of 50 nA the second impulse is suppressed and only the membrane potential at the axon hillock increases slightly. An analysis of the conductances for sodium and potassium ions as well as of the leakage current suggests that the molecular basis for the observed variations in excitability resides in a gradual decrease of the sodium conductance between the cell soma and the small-diameter region of the axon. However, the resting potential in this most excitable axon region is only some 3 mV more positive as compared to the receptor soma. A mathematical formulation is presented for the encoder mechanism in a soma-axon region with varying diameter. Using a slightly modified form of the Hodgkin-Huxley equations the experimentally observed changes in membrane potential and in the time course of the ionic currents can be adequately described by applying a nonlinear cable equation to the inhomogeneous axon. 相似文献
67.
Here, functional AMPA/kainate receptors in human embryonic (5.5–7.5 gestational weeks) and foetal (8–10 gestational weeks) central nervous system tissue, shown by the cobalt labeling method, are reported. Specific agonist-induced cobalt incorporation was detected in brainstem and spinal cord cells, even in the youngest embryo studied. T-AMPA or kainate, but also vegetal toxins such as L-BOAA or acromelate, induced accumulation of cobalt. In contrast, no labeling was observed after exposure to KCl or NMDA. Cobalt labeled cells were particularly prominent in motor regions of brainstem and spinal cord. Co-application of the diuretic agent cyclothiazide, a desensitization blocker at AMPA receptors, dramatically increased the number of stained cells, which was particularly obvious in sensory regions, suggesting different receptor properties in motor versus sensory regions. This is the first study providing evidence for functional AMPA/kainate receptors, permeable to divalent cations, in brainstem and spinal cord at an early stage of human central nervous system development. Since many developmental processes are influenced by the modulation of cytosolic calcium, exposure at critical stages of embryogenesis to food or drug substances modifying the activity of AMPA/kainate receptors may alter brain development. 相似文献
68.
音猬因子的功能受体斑片在培养神经干细胞中的表达 总被引:1,自引:0,他引:1
目的 观察在培养的神经干细胞内是否有发育调控分子———音猬因子 (sonichedgehog)功能受体———斑片 (patched)表达。 方法 神经干细胞克隆在体外培养传代后 ,用patched的特异性引物对培养的神经干细胞进行RT PCR分析 ,PCR产物经克隆测序后 ,用地高辛标记克隆的探针 ,对神经干细胞进行原位杂交分析。 结果 神经干细胞克隆内大量的细胞均可表达sonichedgehog的功能受体patched ,patched阳性细胞间未见明显差别 ,克隆边缘与中央的patched分布也未见明显差别。 结论 sonichedgehog信号传导路可能在神经干细胞的增殖与分化过程中起重要作用。 相似文献
69.
Induction of cyclooxygenase-2 (COX-2) with production of prostaglandins occurs in a wide spectrum of acute and chronic neurodegenerative diseases and is associated with neuronal death. Inhibition of the COX-2 pathway and downstream production of prostaglandins protect neurons in rodent models of cerebral ischemia and neurodegeneration. Recent studies investigating the functions of selected prostaglandin receptor pathways in mediating COX-2 neurotoxicity have demonstrated both toxic and paradoxically neuroprotective effects of several receptors in models of excitotoxicity. In this study, we investigate the functions of additional prostaglandin receptors not previously characterized in organotypic models of glutamate excitotoxicity. We find that PGD2, PGI2, and PGF2α receptors protect motor neurons in an organotypic spinal cord model of amyotrophic lateral sclerosis (ALS). In addition, PGI2 and TXA2 receptors rescue CA1 neurons in an organotypic hippocampal model of N-methyl-d-aspartate excitotoxicity. However, in a model of inflammation induced by lipopolysaccharide, prostaglandin receptors previously found to be protective in excitotoxicity now cause CA1 neuronal death. Taken together, these studies identify novel eicosanoid receptor signaling pathways that mediate neuronal protection in excitotoxic paradigms; these data also support the emerging hypothesis that the toxic/protective effects of eicosanoid signaling on neuronal viability diverge significantly depending on whether excitotoxicity or inflammation predominates as the underlying toxic stimulus. 相似文献
70.
The human non-classical MHC class I molecule HLA-E is a ligand for both an inhibitory NK cell receptor (CD94/NKG2A) and an activating receptor (CD94/NKG2C). To identify HLA-E surface recognized by both receptors, especially to determine if both receptors recognize the same epitope, we made a series of individually Ala-substituted HLA-E proteins and analyzed their binding to CD94/NKG2A orCD94/NKG2C. Eight HLA-E mutations that significantly impaired HLA-E binding to CD94/NKG2A are all found in the top of alpha1/alpha2 domain of HLA-E. These results suggest that CD94/NKG2A binds a HLA-E surface equivalent to a NKG2D binding site on MICA. Of the eight mutations that impaired HLA-E binding to CD94/NKG2A, six significantly impaired HLA-E binding to CD94/NKG2C suggesting that CD94/NKG2C also binds a similar surface of HLA-E. Unexpectedly, the two HLA-E mutations (D69A and H155A) selectively abrogated HLA-E binding to CD94/NKG2A, not largely affected CD94/NKG2C. These results indicate that a mostly shared, but partly distinct set of HLA-E residues is discriminated by the two receptors. 相似文献