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61.
大分子解剖程序,配体分子契合适配和DOCK程序,以及计算化学的其它程序等,已集成为基于受体结构和分子间相互作用的进行分子设计的软件系统,定名为BIOS(Biomolecularinteractionsandorientationsimulator)。BIOS软件可在普通的微机上运行。使用BIOS分别剥离了细胞浆维甲结合蛋白(CRBP)和副睾维甲酸结合蛋白(E-RABP)两种蛋白的配体结合腔,剥离是围绕配体以同样的分子距离进行的。从而得到了芳香性残基分布相似的两个结合腔,其结合位点的几何排布却有相当差别。揭示出的结合腔已用于一系列的维甲类化合物的DOCK研究。E-RABP的结合腔可做为设计新维甲类分子的模板。 相似文献
62.
The contribution of proton spectroscopic (PS) imaging to magnetic resonance (MR) imaging of the liver was assessed at 0.5 T in 55 patients with known or suspected hepatic malignancy. PS images were compared subjectively with T1- and T2-weighted spin-echo (SE) images for hepatic lesion detection and conspicuity. For hepatic metastases (n = 27), PS images were equal to T1-weighted images in lesion detection in 17 patients but showed fewer lesions in five patients and false-negative results in two. When compared with T2-weighted images, PS images depicted more lesions in six patients, an equal number of lesions in 18, and fewer lesions in two. Hepatomas (n = 8) were detected with each sequence in all patients. Hepatomas were often more conspicuous on PS images than on T2-weighted images; they were of equal conspicuity on PS and T1-weighted images in most cases. Whereas fatty infiltration (n = 16) appeared on PS images as areas of low signal intensity similar to that of paraspinal muscle, it produced no detectable abnormality on either T1- or T2-weighted images. PS imaging is inferior to T1-weighted SE imaging in the detection of hepatic metastases. The major role of PS imaging at intermediate field strength is to differentiate focal fatty infiltration from hepatic metastases. 相似文献
63.
64.
Magnetic resonance imaging of the brainstem: normal structure and basic functional anatomy 总被引:2,自引:0,他引:2
Flannigan BD; Bradley WG Jr; Mazziotta JC; Rauschning W; Bentson JR; Lufkin RB; Hieshima GB 《Radiology》1985,154(2):375-383
Normal structure and basic functional anatomy of the brainstem were studied using anatomic sections obtained with a cryomicrotome whole-organ sectioning technique. Major tracts and nuclei were identified and their function summarized. Magnetic resonance imaging of the brainstem was performed on 10 normal volunteers. By comparing these images with the corresponding anatomic sections, normal structures, including major tracts and nuclei, were identified. Knowledge of location and function of clinically important brainstem nuclei and tracts is necessary for optimal magnetic resonance image interpretation. 相似文献
65.
SNAP-25 deficit and hippocampal connectivity in schizophrenia 总被引:3,自引:2,他引:1
Young CE; Arima K; Xie J; Hu L; Beach TG; Falkai P; Honer WG 《Cerebral cortex (New York, N.Y. : 1991)》1998,8(3):261-268
Regional abnormalities of brain connectivity may be an important substrate
for the expression of schizophrenia, a severe form of mental illness. Brain
imaging and postmortem morphometric studies indicate hippocampal structure
is abnormal in schizophrenia. To study molecular components of hippocampal
connectivity the presynaptic proteins SNAP-25 and synaptophysin were
assayed in postmortem samples. Immunocytochemical studies indicated reduced
SNAP-25 immunoreactivity in schizophrenia compared to controls,
particularly in the terminal fields of entorhinal cortex projections.
Although there were no overall changes in synaptophysin immunoreactivity,
in the granule cell layer of the dentate gyrus synaptophysin
immunoreactivity was increased in schizophrenia. These results indicate
that disconnection of a subset of hippocampal circuitry from the entorhinal
cortex, as well as intrinsic changes in hippocampal connectivity, may
contribute to the mechanism of illness in schizophrenia.
相似文献
66.
Introduction to World Kidney Day2011 March10,2011will mark the celebration of the6th World Kidney Day(WKD),an annual event jointly sponsored by the International Society of Nephrology and the International Federation of Kidney Foundations. Since its inception in2006,WKD has grown dramatically to become the most widely celebrated event associated with kidney disease in the world and the most successful effort to raise awareness among both the 相似文献
67.
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69.
Background and purpose:
The ionic mechanisms underlying nitrergic inhibitory junction potentials (IJPs) in gut smooth muscle remain a matter of debate. Recently, it has been reported that opening of TWIK-related K+ channel 1 (TREK-1) K+ channels contributes to the nitrergic IJP in colonic smooth muscle. We investigated the effects of TREK-1 channel blockers on nitrergic neurotransmission in mouse and opossum lower oesophageal sphincter (LOS) circular smooth muscle (CSM).Experimental approach:
The effects of TREK-1 channel blockers were characterized pharmacologically in murine and opossum gut smooth muscle using conventional intracellular and tension recordings.Key results:
In LOS, L-methionine depolarized the resting membrane potential (RMP) but did not inhibit the nitrergic IJP. Cumulative application of theophylline hyperpolarized the RMP and inhibited the nitrergic IJP concentration dependently. The induced membrane hyperpolarization was prevented by pre-application of caffeine, but not by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one. 8-Br-cAMP significantly hyperpolarized membrane potential and increased the amplitude of the nitrergic IJP. In opossum LOS muscle strips, L-methionine increased resting tone but had no effect on nerve-mediated LOS relaxation. On the other hand, theophylline markedly inhibited tone. In CSM from mouse proximal colon, L-methionine caused modest inhibition of nitrergic IJPs.Conclusions and implications:
TREK-1 channels were not involved in the nitrergic IJP in LOS CSM. Not only does L-methionine have no effect on the nitrergic IJP or LOS relaxation, but the effect of theophylline appears to be due to interruption of Ca2+-releasing pathways (i.e. caffeine-like effect) rather than via blockade of TREK-1 channels. 相似文献70.
Mesangial cells in the pathogenesis of progressive glomerular disease in animal models 总被引:2,自引:0,他引:2
J. Floege R. J. Johnson W. G. Couser 《Journal of molecular medicine (Berlin, Germany)》1992,70(9):857-864
Summary Increasing evidence supports a role for glomerular mesangial cell proliferation and overproduction of extracellular matrix by mesangial cells in the development of focal or diffuse glomerulosclerosis. Experimental data obtained mainly in the chronic progressive remnant kidney model and in the acute mesangioproliferative anti-Thy 1.1 glomerulonephritis in rats have shed some insights into the factors governing mesangial cell proliferation and matrix synthesis in vivo. In these experimental models, mesangial cell activation can be demonstrated early in the course of disease as exemplified by the de novo expression by the mesangial cell of a smooth muscle specific actin isotype (i.e., -smooth muscle actin). Following mesangial cell activation, cellular proliferation ensues both in the acute anti-Thy 1.1 model and, to a lesser degree, in the chronic remnant kidney model. While a multitude of mitogens for mesangial cells has been proposed on the basis of in vitro experiments, the factors involved in the regulation of mesangial cell proliferation in vivo remain largely undefined. Three growth factors which may have important roles in the in vivo mesangioproliferative response are platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and transforming growth factor- (TGF-). All three cytokine growth factors are present in various inflammatory cells as well as in mesangial cells themselves, thereby allowing these factors to mediate cell proliferation by either paracrine and/or autocrine pathways. In vivo studies show that PDGF, bFGF, and TGF- participate in the mesangial cell proliferation and/or the mesangial matrix expansion that follows mesangial cell injury with anti-Thy 1.1 antibody. Preliminary evidence also suggests the participation of some of these factors in the mesangial cell proliferation and matrix accumulation that is present in chronic glomerular disease such as in the remnant kidney model. In addition, experiments with transgenic mice suggest the importance of other growth factors, such as growth hormone, in the development of glomerular cell proliferation, matrix expansion, and glomerulosclerosis. Further elucidation of such polypeptide growth factors involved in glomerular pathology may ultimately result in the design of new therapeutic strategies to prevent or treat the progression of renal diseases.Abbreviations bFGF
basic fibroblast growth factor
- PDGF
platelet-derived growth factor
- TGF-
transforming growth factor
- GFR
glomerular filtration rate
- Ig
Immunoglobulin
- PCNA
proliferating cell nuclear antigen 相似文献