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121.
Nobutoshi Komatsu Utaroh Motosugi Shinya Maekawa Kuniaki Shindo Minoru Sakamoto Mitsuaki Sato Akihisa Tatsumi Mika Miura Fumitake Amemiya Yasuhiro Nakayama Taisuke Inoue Mitsuharu Fukasawa Tomoyoshi Uetake Masahiko Ohtaka Tadashi Sato Yasuhiro Asahina Masayuki Kurosaki Namiki Izumi Tomoaki Ichikawa Tsutomu Araki Nobuyuki Enomoto 《Hepatology research》2014,44(13):1339-1346
122.
Masatsugu Ohara Goki Suda Megumi Kimura Osamu Maehara Tomoe Shimazaki Taku Shigesawa Kazuharu Suzuki Akihisa Nakamura Naoki Kawagishi Masato Nakai Takuya Sho Mitsuteru Natsuizaka Kenichi Morikawa Koji Ogawa Tomoe Kobayashi Minoru Uebayashi Ryo Takagi Isao Yokota Tsuyoshi Shimamura Naoya Sakamoto 《Hepatology research》2020,50(6):715-725
123.
Kohei Okita Hiromi Iwahashi Junji Kozawa Yukiyoshi Okauchi Tohru Funahashi Akihisa Imagawa Iichiro Shimomura 《Journal of diabetes investigation.》2014,5(3):305-312
Aims/Introduction
To establish the validity of the plasma glucose disappearance rate (KITT), derived from an insulin‐tolerance test (ITT), for evaluating the insulin sensitivity of patients with type 2 diabetes after insulin therapy.Materials and Methods
In the first arm of the study, 19 patients with poorly controlled diabetes were treated with insulin and underwent an ITT and a euglycemic clamp test (clamp‐IR). The relationship between the insulin resistance index, as assessed by both the clamp‐IR and KITT tests, was examined. In the second arm of the study, the relationships between KITT values and various clinical parameters were investigated in 135 patients with poorly controlled diabetes, after achieving glycemic control with insulin.Results
In study 1, a close correlation between KITT and the average glucose infusion rate during the last 30 min of the standard clamp‐IR test (M‐value) was noted (P < 0.001). In study 2, body mass index (P = 0.0011), waist circumference (P = 0.0004), visceral fat area (P = 0.0011) and the log‐transformed homeostasis model assessment of insulin resistance value (P = 0.0003) were negatively correlated with the log‐transformed KITT. High‐density lipoprotein cholesterol (P = 0.0183), low‐density lipoprotein cholesterol (P = 0.0121) and adiponectin (P = 0.0384) levels were positively correlated with the log‐transformed KITT.Conclusions
The ITT is a valid and useful test for evaluating the insulin sensitivity of patients with diabetes, even after treatment with insulin. 相似文献124.
125.
Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and glucagon secretion in mice
Jung Dae Kim Chitoku Toda Giuseppe D’Agostino Caroline J. Zeiss Ralph J. DiLeone John D. Elsworth Richard G. Kibbey Owen Chan Brandon K. Harvey Christopher T. Richie Mari Savolainen Timo My?h?nen Jin Kwon Jeong Sabrina Diano 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(32):11876-11881
Prolyl endopeptidase (PREP) has been implicated in neuronal functions. Here we report that hypothalamic PREP is predominantly expressed in the ventromedial nucleus (VMH), where it regulates glucose-induced neuronal activation. PREP knockdown mice (Prepgt/gt) exhibited glucose intolerance, decreased fasting insulin, increased fasting glucagon levels, and reduced glucose-induced insulin secretion compared with wild-type controls. Consistent with this, central infusion of a specific PREP inhibitor, , impaired glucose tolerance and decreased insulin levels in wild-type mice. Arguing further for a central mode of action of PREP, isolated pancreatic islets showed no difference in glucose-induced insulin release between Prepgt/gt and wild-type mice. Furthermore, hyperinsulinemic euglycemic clamp studies showed no difference between Prepgt/gt and wild-type control mice. Central PREP regulation of insulin and glucagon secretion appears to be mediated by the autonomic nervous system because Prepgt/gt mice have elevated sympathetic outflow and norepinephrine levels in the pancreas, and propranolol treatment reversed glucose intolerance in these mice. Finally, re-expression of PREP by bilateral VMH injection of adeno-associated virus–PREP reversed the glucose-intolerant phenotype of the Prepgt/gt mice. Taken together, our results unmask a previously unknown player in central regulation of glucose metabolism and pancreatic function.Prolyl endopeptidase (PREP; EC 3.4.21.26) is a highly conserved enzyme ( S170921). In humans and rodents it is highly expressed in the brain (2), including the cortex, striatum, hypothalamus, hippocampus, and amygdala (3–6). The physiological role of PREP remains elusive (7). Many studies have focused on the putative effect of PREP on neuropeptide levels because this enzyme could function to cleave virtually all neuropeptides shorter than 30 amino acids that contain an internal proline residue (8).However, much of our understanding of this enzyme is based on in vitro data. Because PREP’s putative targets regulate a large number of signaling pathways, PREP has the capacity to regulate a variety of cellular tasks.To gain a better understanding of the role of PREP in the hypothalamus, we analyzed the effect of PREP knockdown on hypothalamic mechanisms including glucose and energy metabolism. 相似文献
126.
Distinctive population of Gfap‐expressing neural progenitors arising around the dentate notch migrate and form the granule cell layer in the developing hippocampus 下载免费PDF全文
Tatsunori Seki Toru Sato Keiko Toda Noriko Osumi Tetsuya Imura Seiji Shioda 《The Journal of comparative neurology》2014,522(2):261-283
In the adult hippocampus, granule cells continue to be generated from astrocyte‐like progenitors expressing glial fibrillary acidic protein (GFAP) that differ from embryonic neocortical progenitors. However, during the embryonic period, dentate granule neurons and neocortical pyramidal neurons are derived from the ventricular zone (VZ) of the pallium. Our question is when do GFAP+ progenitors of granule neurons appear in the developing hippocampus during the embryonic period, and how do they form the granule cell layer. The present analysis using Gfap‐GFP transgenic mice shows that the GFP+ distinct cell population first appears in the VZ of the medial pallium at the dorsal edge of the fimbria on embryonic day 13.5. During the perinatal period, they form a migratory stream from the VZ to the developing dentate gyrus, and establish the germinal zones in the migratory stream, and the marginal and hilar regions in the developing dentate gyrus. GFP+ cells in these regions were positive for Sox2 and Ki67, but negative for BLBP. GFP+ cells with Neurogenin2 expression were largely distributed in the VZ, whereas GFP+ cells with Tbr2 and NeuroD expressions were seen in the migratory stream and developing dentate gyrus. Prox1‐expressing GFP+ cells were restricted to the developing dentate gyrus. These results suggest that distinctive Gfap‐expressing progenitors arising around the dentate notch form germinal regions in the migratory stream and the developing dentate gyrus where they differentiate into granule neurons, indicating that distinct astrocyte‐like neural progenitors continue to generate granule neurons, from the beginning of dentate development and throughout life. J. Comp. Neurol. 522:261–283, 2014. © 2013 Wiley Periodicals, Inc. 相似文献
127.
Saito T Muro T Takeda H Hyodo E Ehara S Nakamura Y Hanatani A Shimada K Yoshiyama M 《The American journal of cardiology》2012,110(1):93-97
Recently, an aortic valve area (AVA) index (AVAI) <0.6 cm(2)/m(2) was proposed as an indicator of severe aortic stenosis. The purpose of the present study was to clarify the prognostic value of the AVAI. We identified 103 consecutive asymptomatic patients (mean age 72 ± 11 years) with severe aortic stenosis, defined by an AVA of <1.0 cm(2), who had not undergone aortic valve replacement on initial evaluation. During follow-up (median 36 ± 27 months), 31 aortic valve replacements and 20 cardiac deaths occurred. Multivariate analysis revealed that an AVAI <0.6 cm(2)/m(2) (hazard ratio 2.6, 95% confidence interval 1.1 to 6.3; p = 0.03) and peak aortic jet velocity (Vp) >4.0 m/s (hazard ratio 2.6, 95% confidence interval 1.2 to 5.8; p = 0.02) were associated with cardiac events but that an AVA <0.75 cm(2) was not. The event-free survival of patients with an AVAI of ≥0.6 cm(2)/m(2) was better than that for those with an AVAI <0.6 cm(2)/m(2) (86% vs 41% at 3 years, p <0.01). Furthermore, patients with an AVAI of ≥0.6 cm(2)/m(2) and Vp of ≤4.0 m/s showed an excellent prognosis, but those without these findings had poorer outcomes. In conclusion, AVAI is a powerful predictor of adverse events in asymptomatic patients with severe aortic stenosis. Furthermore, the combination of AVAI and Vp provides additional prognostic information. Watchful observations are required for timely aortic valve replacement in patients with an AVAI of <0.6 cm(2)/m(2) or a Vp >4.0 m/s. 相似文献
128.
129.
Ichiro Kawahara Keisuke Tsutsumi Yuki Matsunaga Hideaki Takahata Tomonori Ono Keisuke Toda Hiroshi Baba 《Acta neurochirurgica》2013,155(8):1543-1548