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The centrosome, an organelle that functions as the major microtubule-organizing center, plays an essential role in the formation of the mitotic spindle and guiding accurate chromosome segregation. Centrosome aberrations are frequently associated with various forms of human cancers and it is thought that defects in this organelle contribute to genomic instability and malignant transformation. We recently identified and characterized a centrosome-localized protein complex that is comprised of Su48 and Nde1. Disruption of the normal function of these proteins leads to abnormal cell division. To extend our understanding of how this protein complex operates, we sought to identify Nde1-interacting molecules by the yeast two-hybrid screening method. Here, we demonstrate that both Nde1 and Su48 can associate with p78/MCRS1, a protein implicated in cancer development. We found that, whereas the majority of p78 localizes to the nucleus as reported in earlier studies, a fraction of the p78 protein can be detected in the centrosome. Moreover, we determined that a region containing the forkhead-associated domain of p78 is involved in association with Nde1 and Su48, as well as in centrosomal localization. We also provide evidence that the association between p78 and Nde1 is regulated by phosphorylation on Nde1. Furthermore, abrogation of the endogenous p78 function by small interfering RNA knockdown causes cell death and a modest delay in mitosis. These results indicate that a subset of the p78 proteins comprises a component of the centrosome and that p78 is essential for cell viability. 相似文献
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Lu ZY Lin ZJ Wang WL Du L Zhu TJ Fang YC Gu QQ Zhu WM 《Journal of natural products》2008,71(4):543-546
In order to search for structurally novel and bioactive natural compounds from microorganisms, a halotolerant fungal strain, Penicillium citrinum B-57, which mainly produces citrinin derivatives, was isolated from sediments collected from the Jilantai salt field. From the ethyl acetate extract of P. citrinum B-57, two new citrinin dimers, pennicitrinone C ( 1) and penicitrinol B ( 2), and 11 known related compounds were isolated and identified by spectroscopic and chemical methods. These compounds showed antioxidative activity against DPPH radicals with IC 50 values ranging from 0.8 to 59 microM. 相似文献
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In patients with coronary artery disease (CAD), coronary blood flow is usually impaired due to imbalanced vasoactive substances such as nitric oxide (NO) and endothelin-1 (ET-1). The study was designed to test the effects of Ginkgo biloba extract (GBE) on the distal left anterior descending coronary artery (LAD) blood flow and plasma NO and ET-1 levels. Eighty CAD patients were randomly assigned to GBE (n = 42) and control (n = 38) groups. The LAD blood flow was assessed non-invasively using Doppler echocardiography at baseline and after 2 weeks. GBE treatment demonstrated a significant improvement in maximal diastolic peak velocity (MDPV), maximal systolic peak velocity (MSPV) and diastolic time velocity integral (DTVI) compared with controls (14.61 +/- 4.51% vs 0.67 +/- 2.66%, 9.03 +/- 4.81% vs 0.34 +/- 2.67% and 14.69 +/- 5.08% vs 0.68 +/- 3.00%, respectively, p < 0.01). NO was increased by 12.42% (p < 0.01), whereas ET-1 was decreased by 5.82% (p < 0.01). The NO/ET-1 ratio was increased by 19.47% (p < 0.01). A linear correlation was confirmed between the percentage change in LAD blood flow and in NO, ET-1 or NO/ET-1 ratio following GBE treatment. The results suggest that GBE treatment in CAD patients led to an increase of LAD blood flow, which might at least be related partly to the restoration of the delicate equilibrium between NO and ET-1. 相似文献
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目的:探究二叶式主动脉瓣中miRNA-195调控瓣膜钙化的可能机制。方法:收集35例接受主动脉瓣置换术患者狭窄的二叶式或三叶式主动脉瓣,通过PCR及Western blot分别检测miRNA-195的表达量、果蝇母源抗皮肤生长因子(drosophila mothers against decapentaplegic 7,SMAD7)的mRNA及蛋白表达量。双荧光素酶法预测miRNA-195的靶基因。在猪瓣膜间质细胞中分别沉默和过表达miRNA-195,检测SMAD7的mRNA表达水平并探究两者的相互关系。在人类瓣膜组织上通过免疫组化染色检测基质金属蛋白酶(matrix metalloproteinase,MMP)-2、MMP-9蛋白水平,通过天狼星红染色检测胶原蛋白水平,通过Von Kossa染色比较钙化程度差异,进而研究钙化相关的功能改变。结果:与狭窄的三叶式主动脉瓣相比,狭窄的二叶式主动脉瓣中miRNA-195表达降低,SMAD7的mRNA和蛋白水平升高。双荧光素酶实验提示SMAD7是miRNA-195的直接靶标。在猪瓣膜间质细胞中沉默miRNA-195引起SMAD7 mRNA水平升高,过表达miRNA-195引起SMAD7 mRNA水平降低。狭窄钙化的二叶式主动脉瓣组织中MMP-2、MMP-9及胶原的表达较狭窄钙化的三叶式主动脉瓣升高。结论:在二叶式主动脉瓣中,下调的miRNA-195促进了SMAD7表达,进而促进细胞外基质的纤维化并最终促进其钙化。 相似文献
106.
Hyper-pigmentation is a common, acquired dermatological skin-disorder manifesting and identifiable as irregular brown or greyish-brown facial discolouration, and sometimes referred to as melanosis, melasma or hypermelanosis. Purpose and Objective: To identify the site of melanin deposition in skin-layers regarding facial hyper-pigmentation, based on a histological study of full-thickness skin-facial biopsies in aged Caucasian-cadavers. Hypothesis: Recalcitrant hyper-pigmentation, is chiefly characterised by hyper-melanosis restricted to the dermal-layer of the integument. Method: The histological features of facial hyper-pigmentation and solar-lentigenes were evaluated in a pilot-study of 5-randomly selected Caucasian-cadavers with pigmentation (15 facial biopsies), ranging in age between 75 and 102 years (mean 77-years). Selection-criteria included, both genders, age 〉 75, focal and confluent hyper-pigmented lesions, involving sun-exposed areas of skin (centrifacial, scalp, malar, mandibular and cervical). Study groups included (Grp-1: Control skin-histology in otherwise normal aged, human-cadavers; Grp-2: Histology of pigmented facial skin-lesions in man; Grp-3: Comparative histological skin-controls in non-human primates). No obvious hepatic disease was evident in the cohort studied. Twenty-five histological controls were obtained from non-pigmented areas. Histological evaluation of full-thickness skin-biopsies (including the lesion, edge and peri-]esion skin), was under a Leitz~-light-microscope, and staining included H&E, Masson-trichrome, Masson-fontana, Alcian-blue and Verhoef technology. Histological-scoring used was on histological deposition of melanin in skin-layers: epidermal, dermal, mixed, and indeterminate melanin-deposition (score 1-4). Controls included cadaveric skin-biopsies of human races of colour and non-human primate, Cercopethicus Aethiops (latter is known to have predominantly dermal-melanin deposition). Pigmented and non-pigmented areas were compared in both species. Results: The majority of clinically visible individual and confluent areas of hyper-pigmentation studied were maeroscopically present on the forehead, frontal scalp in hair-receded cadavers, molar and temporal zones. Histologically, documented features of age-related changes without pigment were present in almost all the embalmed cadaver-skins, with a melanin-score of 1. Computer enhanced skin geometry and biometrics confirmed the presence of an aged-skin, pigmentation and features of solar damage. The human embalmed-tissue was well preserved and minimal autolytic changes were present. Special stains of full-thickness biopsies (Masson-Fontana), showed that melanin in the subhuman-primate is lodged in the deep dermis (reticular dermis), within the extra-cellular matrix (ECM) and superficial to the hypodermal adipose-tissue (melanin-score 3). Fifteen pigmented lesions studied in five (5) aged-cadavers (forehead, molar and mandibular areas) all showed predominantly epidermal-deposition of melanin in the basal, suprabasal and stratum corneum with tiny focal areas of dermal melanosis in single-cell macrophages in the papillary-dermis but not reticular-dermis (melanin-score 2). A melanin-deposition localization ratio of epidermis to dermis was approximately 98 to 2% in cadavers with hyper-pigmentation. Conclusion: The skin-strata localization of the melanin with regards hyper-pigmentation of the face and forehead in this aged, human adult Caucasian, cadaveric-study, was predominantly in the epidermis and sparse in the papillary dermis. 相似文献
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