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11.
目的研究白藜芦醇(Res)通过影响肌球蛋白轻链激酶(MLCK)在肝脏中表达水平抑制原发性肝癌的增生。方法采用口服饮水中含0.9 mmol.L-1二乙基亚硝胺10周诱发原发性肝肿瘤;20周后,治疗组大鼠每天给予肌肉注射Res 50 mg.kg-16周;26周后,处死大鼠,计数肝表面癌结节数,称量和计算体重、肝重,肝/体重比,测定血清中甲胎蛋白的变化,观察大鼠肝脏的病理改变;用免疫组化和Westernblot法检测Res对MLCK的表达影响,用细胞凋亡试剂盒检测Res诱导肿瘤细胞的凋亡。结果 Res治疗组大鼠和模型组大鼠相比,体重增加,肝肿瘤结节数和肝/体重比和血清甲胎蛋白值减少或降低(P<0.05)。模型组大鼠肝组织MLCK的表达水平明显增加,而Res治疗可逆转MLCK的过表达水平,并诱导肿瘤细胞凋亡。结论 Res通过下调肝组织MLCK的表达水平诱导凋亡,抑制大鼠肝肿瘤细胞的增生。 相似文献
12.
Zhiyi Wei Xiaotian Liu Cong Yu Mingjie Zhang 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(28):11314-11319
Class V myosins (MyoV), the most studied unconventional myosins, recognize numerous cargos mainly via the motor’s globular tail domain (GTD). Little is known regarding how MyoV-GTD recognizes such a diverse array of cargos specifically. Here, we solved the crystal structures of MyoVa-GTD in its apo-form and in complex with two distinct cargos, melanophilin and Rab interacting lysosomal protein-like 2. The apo-MyoVa-GTD structure indicates that most mutations found in patients with Griscelli syndrome, microvillus inclusion disease, or cancers or in “dilute” rodents likely impair the folding of GTD. The MyoVa-GTD/cargo complex structure reveals two distinct cargo-binding surfaces, one primarily via charge–charge interaction and the other mainly via hydrophobic interactions. Structural and biochemical analysis reveal the specific cargo-binding specificities of various isoforms of mammalian MyoV as well as very different cargo recognition mechanisms of MyoV between yeast and higher eukaryotes. The MyoVa-GTD structures resolved here provide a framework for future functional studies of vertebrate class V myosins. 相似文献
13.
Neonatal circulatory transition is dependent upon tightly regulated pulmonary circuit relaxation. Persistent pulmonary hypertension of the newborn (PPHN) is characterized by pulmonary arterial myocyte relaxation failure. We examined the effect of short course (72 hour) in vivo normobaric hypoxia in newborn swine on smooth muscle contractile enzyme activity and regulatory phosphoprotein abundance, in tissue homogenates of 2nd to 4th generation pulmonary arteries. Myosin light chain kinase (MLCK) and phosphatase (MLCP) protein contents were unchanged in hypoxic pulmonary arteries compared to controls. MLCP activity increased in normoxic animals from birth to day 3. This was ablated by hypoxia; phosphatase activity, measured as in vitro myosin light chain dephosphorylation, was decreased significantly (P < 0.005) in the hypoxic group. Inhibitory site phosphorylations of MLCP myosin binding subunit at threonines 696 and 850 were similar in both hypoxic and normoxic subjects, suggesting that downregulation of MLCP in hypoxia does not involve this pathway. However, content of regulatory protein CPI-17 (protein kinase C-related phosphatase inhibitor) increased from birth in hypoxic subjects (P < 0.05); active (phosphorylated) CPI-17 protein abundance declined after birth in normals, but increased in hypoxic arteries (P < 0.05). This corresponded with the decrease in phosphatase activity. We speculate that CPI-17 may play a role in myosin phosphatase upregulation during neonatal circulatory transition, and in hypoxic inhibition of pulmonary phosphatase activity in PPHN. 相似文献
14.
J Wikman-Coffelt R Walsh C Fenner T Kamiyama A Salel D T Mason 《Journal of molecular and cellular cardiology》1976,8(4):263-270
Left ventricular myosin ATPase activity, expressed as enzymatic Vmax values, was analyzed in dogs subjected to severe left ventricular pressure overload (aortic stenosis). K+ and Ca2+ activated myosin ATPase activities in the left ventricle (LV) were significantly depressed (P < .01) in the experimental animals. For normal K+ activated myosin the Vmax values in micromoles of Pi per mg per min were: right ventricle 2.10; left ventricle, 2.84. For Ca2+ activated myosin the Vmax values were: right ventricle, 0.77; left ventricle 0.97, when assayed at 37°C. Myosin enzymatic activity in the left ventricle progressively declined following severe aortic banding, reaching a value similar to that observed for normal right ventricular myosin; NH4+ activated left ventricular myosin ATPase activity remained unchanged (7.20 ± 0.4 μmol PO4/mg.min). Left ventricular myosin from the hearts subject to severe stress simulated normal right ventricular myosin in ATPase activity, chain proportions and degree of calcium binding, Normal left ventricular myosin contained approximately 10% of the myosin protein concentration in the light chains; myosin from the left ventricles of the hemodynamically overloaded hearts contained 20% of the myosin protein concentration in the light chains (P < .001). With only one of the myosin light chains binding calcium left ventricular myosin from the stressed hypertrophied tissue bound approximately 2 mol Ca2+ mol?1 myosin similar to myosin of the normal right ventricle; normal left ventricular myosin bound approximately 1 mol of Ca2+ mol?1 myosin. 相似文献
15.
Clint L. Miller Amy R. Kontorovich Ke Hao Lijiang Ma Conrad Iyegbe Johan L.M. Björkegren Jason C. Kovacic 《Journal of the American College of Cardiology》2021,77(20):2531-2550
In this second of a 5-part Focus Seminar series, we focus on precision medicine in the context of vascular disease. The most common vascular disease worldwide is atherosclerosis, which is the primary cause of coronary artery disease, peripheral vascular disease, and a large proportion of strokes and other disorders. Atherosclerosis is a complex genetic disease that likely involves many hundreds to thousands of single nucleotide polymorphisms, each with a relatively modest effect for causing disease. Conversely, although less prevalent, there are many vascular disorders that typically involve only a single genetic change, but these changes can often have a profound effect that is sufficient to cause disease. These are termed “Mendelian vascular diseases,” which include Marfan and Loeys-Dietz syndromes. Given the very different genetic basis of atherosclerosis versus Mendelian vascular diseases, this article was divided into 2 parts to cover the most promising precision medicine approaches for these disease types. 相似文献
16.
目的:采用17β-雌二醇联合去势建立大鼠慢性非细菌性前列腺炎模型,检测膀胱逼尿肌蛋白在慢性前列腺炎大鼠膀胱的表达。方法取2月龄 SD 雄性大鼠60只随机分为6组,每组10只,即:空白对照组、生理盐水组、假手术组、单纯17β-雌二醇组、单纯去势组、17β-雌二醇联合去势组。HE 染色判定大鼠慢性前列腺炎模型建造成功后,采用 SP 免疫组化法、Western blot 检测6组大鼠膀胱组织肌动蛋白(α-actin)、肌球蛋白(MLC 2)及高分子量钙调素结合蛋白(h-cad)表达的差异。结果免疫组化结果显示17β-雌二醇联合去势组中α-actin、MLC 2、h-cad 蛋白表达增多,Western blot 显示α-actin 在各组的表达,与空白对照组相比,生理盐水组、假手术组、单纯17β-雌二醇组、单纯去势组联合去势组差异有统计学意义。 MLC 2、h-cad 在各组的表达与空白对照组相比,生理盐水组、假手术组差异无统计学意义,单纯17β-雌二醇组、单纯去势组、联合去势组差异有统计学意义。结论α-actin、MLC 2、h-cad 表达变化可能参与慢性前列腺炎排尿相关症状的发病。 相似文献
17.
Ana Martins Figueiredo Pedro Barbacena Ana Russo Silvia Vaccaro Daniela Ramalho Andreia Pena Aida Pires Lima Rita Rua Ferreira Marta Alves Fidalgo Fatima El-Marjou Yulia Carvalho Francisca Ferreira Vasconcelos Ana-Maria Lennon-Dumnil Danijela Matic Vignjevic Claudio Areias Franco 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(18)
18.
19.
Wei Wu Qiaobing Huang Jingxia Miao Mingjia Xiao Hongxia Liu Kesen Zhao Ming Zhao 《Burns : journal of the International Society for Burn Injuries》2013
We previously reported Rho kinase is involved in vessel hyper-permeability caused by burns. Here we further explore the Rho kinase downstream signaling, it is found that its specific inhibitor Y27632 significantly diminishes the activation of JNK and p38 MAPKs but not ERK that induced by serum from burned rats (burn-serum). JNK activation was found involved in the expression of HUVEC adhesion molecules following thermal injury, although not in the process of stress fiber formation. Inhibition of various MAPKs by specific inhibitors showed that SB203580 (inhibitor of p38), but neither SP600125 (inhibitor of JNK) nor PD98059 (inhibitor of ERK), abolish activation of the p38 downstream kinase MK2. Demonstration of stress fibers by fluorescent-labeled phalloidin showed that inhibition of MK2, either by its specific inhibitor or by dominant negative adeno-viral-carried constructs, significantly reduced burn-serum-induced HUVEC stress-fiber formation, while inhibition of another downstream p38 MAPK kinase, PRAK, had no such effects. Transfection of dominant negative adeno-viral MK2 (Ad-MK2(A)) significantly inhibited thermal injury-induced blood vessel hyper-permeability in rats and, moreover, prolonged the survival of burned rats beyond 72 h following thermal injury. One of the mechanisms behind these phenomena is that Ad-MK2(A) causes a significant depression of burn-serum-induced HSP27-phosphorylation, while the adeno-viral transported dominant negative PRAK (Ad-PRAK(A)) does not block. Although the effect of blockade of MK2 through its adeno-viral approach requires further study and investigation of alternatives to know for sure, we may have found a new pathway behind thermal-injury-induced blood vessel hyper-permeability, namely: Rho kinase > p38 > MK2 > HSP27. 相似文献
20.
Heat shock transcription factor 1‐associated expression of slow myosin heavy chain in mouse soleus muscle in response to unloading with or without reloading 下载免费PDF全文