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Gelena V. Lifshitz Dmitry D. Zhdanov Anastasia V. Lokhonina Daria D. Eliseeva Elena Y. Lyssuck Igor A. Zavalishin 《Autoimmunity》2016,49(6):388-396
Multiple sclerosis (MS) is an autoimmune disease characterized by defect in regulatory function of CD4+CD25+ T cells. We demonstrated difference in proportion of regulatory T cells CD4+CD25+FoxP3+CD127low (Tregs) within the same patients’ relapse and remission. Proportion of peripheral Tregs (pTregs) dropped almost two times in the relapse compare to remission. Levels of pTregs in patients’ remission were lower than in healthy donors. Suppressive ability of pTregs was decreased in MS patients compared to healthy donors. Injections of expanded ex vivo autologous Tregs (eTregs) could be helpful in bringing up the level of Tregs in patients’ blood. We developed a simple method for ex vivo expansion of autologous Tregs within a short period of time. The final pool of cells consisted of 90-95% eTregs. When we started the culture with 10-20?×?106 CD4+ T cells, we yield 300-400?×?106 eTregs in a week. Expression of FoxP3 and Helios was calculated by two methods. Expanded ex vivo patients’ and donors’ Tregs were characterized by increased from three to five times expression of FoxP3, as well as almost doubled Helios expression. Peripheral Tregs in MS patients have decreased demethylation of FoxP3 gene promoter in comparison with donors. On the contrary, eTregs showed stable up-regulated demethylation without difference between MS patients and donors. MS patients’ and donors’ eTregs have much more suppressive ability than pTregs. Our data showed that eTregs can be applied as immunotherapy for MS patients and other autoimmune diseases if further investigated. 相似文献
105.
Smooth muscle myosin filament assembly under control of a kinase-related protein (KRP) and caldesmon
Kudryashov DS Vorotnikov AV Dudnakova TV Stepanova OV Lukas TJ Sellers JR Watterson DM Shirinsky VP 《Journal of muscle research and cell motility》2002,23(4):341-351
Kinase-related protein (KRP) and caldesmon are abundant myosin-binding proteins of smooth muscle. KRP induces the assembly
of unphosphorylated smooth muscle myosin filaments in the presence of ATP by promoting the unfolded state of myosin. Based
upon electron microscopy data, it was suggested that caldesmon also possessed a KRP-like activity (Katayama et al., 1995, J Biol Chem 270: 3919–3925). However, the nature of its activity remains obscure since caldesmon does not affect the equilibrium between
the folded and unfolded state of myosin. Therefore, to gain some insight into this problem we compared the effects of KRP
and caldesmon, separately, and together on myosin filaments using turbidity measurements, protein sedimentation and electron
microscopy. Turbidity assays demonstrated that KRP reduced myosin filament aggregation, while caldesmon had no effect. Additionally,
neither caldesmon nor its N-terminal myosin binding domain (N152) induced myosin polymerization at subthreshold Mg2+ concentrations in the presence of ATP, whereas the filament promoting action of KRP was enhanced by Mg2+. Moreover, the amino-terminal myosin binding fragment of caldesmon, like the whole protein, antagonizes Mg2+-induced myosin filament formation. In electron microscopy experiments, caldesmon shortened myosin filaments in the presence
of Mg2+ and KRP, but N152 failed to change their appearance from control. Therefore, the primary distinction between caldesmon and
KRP appears to be that caldesmon interacts with myosin to limit filament extension, while KRP induces filament propagation
into defined polymers. Transfection of tagged-KRP into fibroblasts and overlay of fibroblast cytoskeletons with Cy3KRP demonstrated
that KRP colocalizes with myosin structures in vivo. We propose a new model that through their independent binding to myosin and differential effects on myosin dynamics, caldesmon
and KRP can, in concert, control the length and polymerization state of myosin filaments.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
106.
Diana S. Novikova Tatiana V. Popkova Galina V. Lukina Elena L. Luchikhina Dmitry E. Karateev Alexander V. Volkov Alexander A. Novikov Elena N. Aleksandrova Evgeny L. Nasonov 《Journal of Korean medical science》2016,31(2):202-207
The aim of the study was to examine lipid profiles, arterial stiffness (AS), carotid intima-media thickness (cIMT), in 55 women with RA without overt cardiovascular disease (СVD) treated with rituximab (RTX).The following parameters were recorded before and 24 weeks after RTX therapy (2 infusions of 500 or 1,000 mg RTX intravenously, fortnightly): plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, DAS 28-ESR, serum C-reactive protein (CRP), RF IgM, AS (SI - stiffness index, RI – reflection index) by digital volume pulse contour analysis (Micro Medical, UK), and common cIMT by high-resolution B-mode carotid ultrasound. Based on the European League Against Rheumatism (EULAR) criteria, patients were divided into two groups: 1) moderate/good response to RTX therapy after 24 weeks (41 patients, 75%), 2) no response to RTX therapy (14 patients, 25%). Effective RTX therapy resulted in 9% increase in TC, 23% increase in HDL-C and 14% decrease in atherogenic index, 57% decrease in SI and 24% decrease in RI. We observed a 9% decrease of cIMTmax at 24 weeks. The improvement of cardiovascular parameters was accompanied by statistically significant decreases of CRP, ESR, RF IgM and DAS 28 in group 1 (P < 0.05). There were not significant changes in lipid profile, AS parameters, and cIMT in group 2. Two infusions of RTX in case of moderate/good EULAR effect of therapy exerted favorable effects on lipid profile, AS and cIMT in women with RA without overt CVD. 相似文献
107.
Retiform perineurioma is a rare distinct histologic subtype of benign soft tissue perineurioma. We report 1 case of retiform perineurioma with a superficial invasion of the adjacent skeletal muscle. The patient was a 34-year-old woman with a neoplasm located between the deltoid muscle and the biceps. Histologically, the tumor was nonencapsulated, composed exclusively of perineurial cells without cytologic and tissue atypia. There were focal areas in which the neoplastic cells infiltrated the muscle tissue, widely separating the bundles. This case may represent a diagnostic pitfall as it can be confused with a malignant perineurioma. 相似文献
108.
Genetic basis for individual variations in pain perception and the development of a chronic pain condition 总被引:11,自引:0,他引:11
Diatchenko L Slade GD Nackley AG Bhalang K Sigurdsson A Belfer I Goldman D Xu K Shabalina SA Shagin D Max MB Makarov SS Maixner W 《Human molecular genetics》2005,14(1):135-143
Pain sensitivity varies substantially among humans. A significantpart of the human population develops chronic pain conditionsthat are characterized by heightened pain sensitivity. We identifiedthree genetic variants (haplotypes) of the gene encoding catecholamine-O-methyltransferase(COMT) that we designated as low pain sensitivity (LPS), averagepain sensitivity (APS) and high pain sensitivity (HPS). We showthat these haplotypes encompass 96% of the human population,and five combinations of these haplotypes are strongly associated(P=0.0004) with variation in the sensitivity to experimentalpain. The presence of even a single LPS haplotype diminishes,by as much as 2.3 times, the risk of developing myogenous temporomandibularjoint disorder (TMD), a common musculoskeletal pain condition.The LPS haplotype produces much higher levels of COMT enzymaticactivity when compared with the APS or HPS haplotypes. Inhibitionof COMT in the rat results in a profound increase in pain sensitivity.Thus, COMT activity substantially influences pain sensitivity,and the three major haplotypes determine COMT activity in humansthat inversely correlates with pain sensitivity and the riskof developing TMD. 相似文献
109.
Hadravsky L Skalova A Kacerovska D Kazakov DV Chudacek Z Michal M 《Virchows Archiv : an international journal of pathology》2012,460(2):203-209
We present 45 patients with angiomatoid polyps of the nasal and paranasal regions (APNPRs), which are underrecognized lesions
which may cause considerable diagnostic difficulties. There were 32 men and 13 women in our series. The average age at diagnosis
was 49 years in men and 54.3 years in women. Locations were known in 41 cases and included the nasal septum (14), maxillary
sinus (12), ethmoid sinuses (5), lateral wall of the nasal cavity (5), sphenoid sinus (1), and nasal cavity, not otherwise
specified (4). X-ray or computed tomography was performed in 19 cases and revealed bone erosions/deviations in four cases.
Initial misdiagnoses submitted by referring pathologists were reported in 20/32 of the consultation cases. Our study confirms
that APNPRs are benign lesions which often recur and sometimes multiple recurrences are seen. APNPRs sometimes cause severe
changes of the skeletal bones especially in recurrent lesions. Awareness of the above described features and familiarity with
the clinical presentation of APNPRs is the best way to avoid a misdiagnosis. 相似文献
110.
Gol'dshtein DV Vikhlyantseva EV Sakharova NK Maevskii EI Pogorelov AG Uchitel' ML 《Bulletin of experimental biology and medicine》2004,138(2):205-206
We propose a method of evaluation of anticlimacteric efficiency of a drug by its effect on the estrous cycle. The study was carried out on 9-month-old mice with retained, but notably reduced reproductive function. Analysis of the cell components of the estrous cycle was carried out on histological preparations of vaginal smears. 相似文献