全文获取类型
收费全文 | 5464篇 |
免费 | 274篇 |
国内免费 | 24篇 |
专业分类
耳鼻咽喉 | 40篇 |
儿科学 | 70篇 |
妇产科学 | 47篇 |
基础医学 | 620篇 |
口腔科学 | 100篇 |
临床医学 | 274篇 |
内科学 | 1174篇 |
皮肤病学 | 387篇 |
神经病学 | 482篇 |
特种医学 | 134篇 |
外科学 | 1005篇 |
综合类 | 16篇 |
预防医学 | 177篇 |
眼科学 | 78篇 |
药学 | 292篇 |
中国医学 | 12篇 |
肿瘤学 | 854篇 |
出版年
2023年 | 33篇 |
2022年 | 56篇 |
2021年 | 106篇 |
2020年 | 55篇 |
2019年 | 61篇 |
2018年 | 126篇 |
2017年 | 95篇 |
2016年 | 124篇 |
2015年 | 128篇 |
2014年 | 152篇 |
2013年 | 181篇 |
2012年 | 265篇 |
2011年 | 288篇 |
2010年 | 126篇 |
2009年 | 158篇 |
2008年 | 236篇 |
2007年 | 218篇 |
2006年 | 258篇 |
2005年 | 241篇 |
2004年 | 225篇 |
2003年 | 229篇 |
2002年 | 241篇 |
2001年 | 203篇 |
2000年 | 190篇 |
1999年 | 218篇 |
1998年 | 72篇 |
1997年 | 62篇 |
1996年 | 64篇 |
1995年 | 59篇 |
1994年 | 44篇 |
1993年 | 46篇 |
1992年 | 143篇 |
1991年 | 108篇 |
1990年 | 125篇 |
1989年 | 139篇 |
1988年 | 85篇 |
1987年 | 79篇 |
1986年 | 60篇 |
1985年 | 77篇 |
1984年 | 38篇 |
1983年 | 38篇 |
1981年 | 24篇 |
1980年 | 19篇 |
1979年 | 41篇 |
1978年 | 25篇 |
1977年 | 25篇 |
1974年 | 17篇 |
1971年 | 18篇 |
1969年 | 16篇 |
1968年 | 18篇 |
排序方式: 共有5762条查询结果,搜索用时 31 毫秒
61.
Kouya Hattori Masahiro Akiyama Natsumi Seki Kyosuke Yakabe Koji Hase Yun-Gi Kim 《Nutrients》2021,13(6)
While poorly-absorbed sugar alcohols such as sorbitol are widely used as sweeteners, they may induce diarrhea in some individuals. However, the factors which determine an individual’s susceptibility to sugar alcohol-induced diarrhea remain unknown. Here, we show that specific gut bacteria are involved in the suppression of sorbitol-induced diarrhea. Based on 16S rDNA analysis, the abundance of Enterobacteriaceae bacteria increased in response to sorbitol consumption. We found that Escherichia coli of the family Enterobacteriaceae degraded sorbitol and suppressed sorbitol-induced diarrhea. Finally, we showed that the metabolism of sorbitol by the E. coli sugar phosphotransferase system helped suppress sorbitol-induced diarrhea. Therefore, gut microbiota prevented sugar alcohol-induced diarrhea by degrading sorbitol in the gut. The identification of the gut bacteria which respond to and degrade sugar alcohols in the intestine has implications for microbiome science, processed food science, and public health. 相似文献
62.
Kanan Bando Toshinobu Kuroishi Hiroyuki Tada Takefumi Oizumi Yukinori Tanaka Tetsu Takahashi Itaru Mizoguchi Shunji Sugawara Yasuo Endo 《Journal of bone and mineral research》2021,36(9):1866-1878
Among the bisphosphonates (BPs), nitrogen-containing BPs (N-BPs) have much stronger anti–bone-resorptive actions than non-N–BPs. However, N-BPs have various side effects such as acute influenza-like reactions after their initial administration and osteonecrosis of the jawbones after repeated administration. The mechanisms underlying such effects remain unclear. To overcome these problems, it is important to profile the inflammatory nature of N-BPs. Here, we analyzed the inflammatory reactions induced in mouse ear pinnae by the N-BPs alendronate (Ale) and zoledronate (Zol). We found the following: (i) Ale and Zol each induced two phases of inflammation (early weak and late strong ear swelling); (ii) both phases were augmented by lipopolysaccharides (LPSs; cell-surface constituent of gram-negative bacteria, including oral bacteria), but prevented by inhibitors of the phosphate transporters of solute carrier 20/34 (SLC20/SLC34); (iii) macrophages and neutrophils were involved in both phases of Ale+LPS–induced ear-swelling; (iv) Ale increased or tended to increase various cytokines, and LPS augmented these effects, especially that on interleukin 1β (IL-1β); (v) adenosine triphosphate (ATP) was involved in both phases, and Ale alone or Ale+LPS increased ATP in ear pinnae; (vi) the augmented late-phase swelling induced by Ale+LPS depended on both IL-1 and neutrophil extracellular traps (NETs; neutrophil-derived net-like complexes); (vii) neutrophils, together with macrophages and dendritic cells, also functioned as IL-1β–producing cells, and upon stimulation with IL-1β, neutrophils produced NETs; (viii) stimulation of the purinergic 2X7 (P2X7) receptors by ATP induced IL-1β in ear pinnae; (ix) NET formation by Ale+LPS was confirmed in gingiva, too. These results suggest that (i) N-BPs induce both early-phase and late-phase inflammation via ATP-production and P2X7 receptor stimulation; (ii) N-BPs and LPS induce mutually augmenting responses both early and late phases via ATP-mediated IL-1β production by neutrophils, macrophages, and/or dendritic cells; and (iii) NET production by IL-1β–stimulated neutrophils may mediate the late phase, leading to prolonged inflammation. These results are discussed in relation to the side effects seen in patients treated with N-BPs. © 2021 American Society for Bone and Mineral Research (ASBMR). 相似文献
63.
Kazu Matsumoto Daichi Ishimaru Hiroyasu Ogawa Shingo Komura Katsuji Shimizu Haruhiko Akiyama 《Journal of orthopaedic science》2021,26(3):483-486
BackgroundsExostosin-1 (EXT1) and exostosin-2 (EXT2) cause multiple osteochondromas (MO). In this study, we investigated the correlation between forearm deformity and mutant EXTs in Japanese families with MO.MethodsWe evaluated 112 patients in 71 families with MO. Genomic DNA was isolated from peripheral blood leucocytes. Of these, 28 patients were selected and underwent radiography for their forearms since they had gross forearm deformities. We measured the radial articular angle (RAA), ulna variance (UV), carpal slip (CS), and percentage of radial bowing (%RB) to compare between patients with mutant EXT1 or EXT2 and those with missense or other mutations using Student's t-test.ResultsTwenty-two (78.6%) and 6 (11.4%) out of 28 patients had mutations in EXT1 and EXT2, respectively. Nine (32.1%) and 19 (67.9%) of the 28 patients had missense and other mutations, respectively. The mean age of patients with EXT1 and EXT2 were 25.9 ± 20.3 and 33.5 ± 25.4 years, respectively and those with missense mutation and other mutations were 28.7 ± 27.0 and 24.6 ± 17.0 years, respectively. There were no significant differences in RAA, UV, and RB between patients harbouring mutant EXT1 or EXT2 (RAA, 40.1 ± 8.7 and 31.5 ± 13.9°; UV, ?2.7 ± 5.7 and ?3.1 ± 3.7 mm; %RB, 8.6 ± 1.5 and 8.3 ± 2.0%). CS was significantly greater in patients with mutant EXT1 than that in those with mutant EXT2 (EXT1, 44.1 ± 16.8%; EXT2, 18.6 ± 14.0%). There were no significant differences in RAA, UV, CS and %RB between patients with missense and other mutations.ConclusionsPatients with mutant EXT1 displayed greater CS than patients with mutant EXT2, indicating that patients with MO harbouring EXT1 mutations sustain more severe ulnar drift deformities than those with EXT2 mutations. 相似文献
64.
Wada Takehiko Ishimoto Takuji Nakaya Izaya Kawaguchi Takehiko Sofue Tadashi Shimizu Sayaka Kurita Noriaki Sasaki Sho Nishiwaki Hiroki Koizumi Masahiro Saito Shoji Nishibori Nobuhiro Oe Yuji Yoshida Mai Miyaoka Yoshitaka Akiyama Shin’ichi Itano Yuya Okazaki Masaki Ozeki Takaya Ichikawa Daisuke Oguchi Hideyo Kohsaka Satoshi Kosaka Shiho Kataoka Yuki Shima Hideaki Shirai Sayuri Sugiyama Kazuhiro Suzuki Tomo Son Daisuke Tanaka Tomomi Nango Eishu Niihata Kakuya Nishijima Yoko Nozu Kandai Hasegawa Midori Miyata Rei Yazawa Masahiko Yamamoto Yoshihiro Yamamoto Ryohei Shibagaki Yugo Furuichi Kengo Okada Hirokazu Narita Ichiei 《Clinical and experimental nephrology》2021,25(12):1277-1285
Clinical and Experimental Nephrology - 相似文献
65.
66.
67.
Summary Silver staining by a modified Bielschowsky's technique and immunostaining for -amyloid protein BAP have revealed the occurrence of diffuse amyloid deposits bilaterally in the presubiculum in each of fourteen Alzheimer's disease cases examined. Observations on serial blocks show these deposits to be localized in the parvopyramidal layer of the presubiculum proper and the transsubiculum. They are also observed in the cellular islands within the molecular layer of the subiculum but not in the parasubiculum. These amyloid deposits are not accompanied by neurofibrillary tangles, neuropil threads, or the aggregated microglial reaction which is characteristically associated with classic senile plaques. Convergence of input from limbic and cortical areas might play a significant role in the formation of these diffuse amyloid deposits.Supported by grants from the MRC of Canada, the Alzheimer's Society of B.C., the American Health Assistance Foundation and the McLean Foundation 相似文献
68.
Akitaka Yamasaki Kumiko Maruyama-Takahashi Kento Nishida Shogo Okazaki Kouki Okita Yasutoshi Akiyama Hideaki Suzuki Yuichi Endo Kazue Masuko Takashi Masuko Yoshihisa Tomioka 《Genes to cells : devoted to molecular & cellular mechanisms》2023,28(5):374-382
Human epidermal growth factor receptor (HER) family proteins are currently major targets of therapeutic monoclonal antibodies against various epithelial cancers. However, the resistance of cancer cells to HER family-targeted therapies, which may be caused by cancer heterogeneity and persistent HER phosphorylation, often reduces overall therapeutic effects. We herein showed that a newly discovered molecular complex between CD98 and HER2 affected HER function and cancer cell growth. The immunoprecipitation of the HER2 or HER3 protein from lysates of SKBR3 breast cancer (BrCa) cells revealed the HER2-CD98 or HER3-CD98 complex. The knockdown of CD98 by small interfering RNAs inhibited the phosphorylation of HER2 in SKBR3 cells. A bispecific antibody (BsAb) that recognized the HER2 and CD98 proteins was constructed from a humanized anti-HER2 (SER4) IgG and an anti-CD98 (HBJ127) single chain variable fragment, and this BsAb significantly inhibited the cell growth of SKBR3 cells. Prior to the inhibition of AKT phosphorylation, BsAb inhibited the phosphorylation of HER2, however, significant inhibition of HER2 phosphorylation was not observed in anti-HER2 pertuzumab, trastuzumab, SER4 or anti-CD98 HBJ127 in SKBR3 cells. The dual targeting of HER2 and CD98 has potential as a new therapeutic strategy for BrCa. 相似文献
69.
Ritsuko Akiyama Kunyan Kuang Pablo A. Chiaradía Calvin W. Roberts Jorge Fischbarg 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》1997,235(6):384-387
Background: Anterior chamber miotic solutions are widely used in ophthalmic surgery to induce pupillary contraction. We investigated whether the acetylcholine, carbachol, or mannitol present in perfusing solutions can affect corneal endothelial function. Methods: Freshly dissected deepithelized rabbit corneas were mounted in a Dikstein-Maurice chamber at 36 °C. The endothelial sides were perfused with six solutions: (A) 55 mM (1%) acetylcholine Cl plus modified balanced salts; (B) control for A, with acetylcholine Cl replaced by sucrose; (C) 0.55 mM (0.01%) carbachol Cl plus balanced salts; (D) balanced salts solution (BS; control for C); (E) 3% mannitol plus modified balanced salts; and (F) modified balanced salts (control for E, with mannitol replaced by sucrose). Corneal thickness was followed for 3 h in each experiment. The effect of solution E did not differ from that of solution F. Results: The carbachol-containing solution produced a small increase in corneal thickness compared to the control solution, while the acetylcholine-containing solution resulted in corneal thickness lower than that in control preparations. Conclusion: From these data, acetylcholine is harmless to the endothelium, and may actually stimulate its fluid pump mechanism. Carbachol, on the other hand, appears to have a detrimental effect. 相似文献
70.
Growth suppression of non-small cell lung carcinoma cells by the introduction of the p16(INK4A) gene
The p16(INK4A) gene is frequently inactivated in nonsmall cell lung carcinoma (NSCLC) by either mutations, deletions or DNA methylations. To assess the biological significance of p16(INK4A) inactivation in the development of NSCLC, full-length p16(INK4A) cDNA was introduced into NSCLC cell lines, A549 and H322, in which p16(INK4A) was homozygously deleted. NSCLC cells transfected with the p16(INK4A) expression vector formed colonies in 20-68% of those with a control vector, and exogenous p16(INK4A) protein was expressed in 4 of 68 A549-derived clones and none of 29 H322-derived clones, respectively. A549-derived clones which stably expressed the exogenous p16(INK4A) gene showed significant decrease in growth rate in vitro and tumorigenicity in vivo in proportion to the level of p16(INK4A) expression. Furthermore, the cell cycle of these cells significantly delayed with accumulation of cells in G1 phase. Micro-injection of p16(INK4A) expression vector also revealed that p16(INK4A) blocked S phase entry in both A549 and H322 cells. These results suggest that the restoration of the p16(INK4A) function suppresses the growth of NSCLC cells by induction of G1 arrest in the cells. Therefore, inactivation of p16(INK4A) may play an important role in the enhancement of unregulated NSCLC growth in vivo. 相似文献