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61.
Mai Kikumoto Shuichiro Neshige Takeo Shishido Hiroki Ueno Shiro Aoki Koji Iida Hirofumi Maruyama 《Internal medicine (Tokyo, Japan)》2022,61(8):1237
We evaluated a 39-year-old pregnant woman with right temporal lobe epilepsy. During the second trimester, seizure deterioration was responsive to an increased daily dose of levetiracetam (LEV). However, immediately after delivery, new non-habitual seizures emerged along with a sharply increased LEV concentration. The frequency of habitual seizures also slightly increased. The non-habitual seizures completely disappeared, and the frequency of the habitual seizures improved to the baseline level after the LEV dosage was reduced. Thus, a paradoxical effect of an increased LEV blood concentration was assumed to be a potential cause of these events. Peripartum pharmacokinetic fluctuations in LEV levels should be monitored carefully. 相似文献
62.
Yang Liu Yoshifumi Baba Takatsugu Ishimoto Hiroyasu Tsutsuki Tianli Zhang Daichi Nomoto Kazuo Okadome Kensuke Yamamura Kazuto Harada Kojiro Eto Yukiharu Hiyoshi Masaaki Iwatsuki Yohei Nagai Shiro Iwagami Yuji Miyamoto Naoya Yoshida Yoshihiro Komohara Masaki Ohmuraya Xiaoming Wang Jaffer A. Ajani Tomohiro Sawa Hideo Baba 《British journal of cancer》2021,124(5):963
Background Fusobacterium nucleatum (F. nucleatum) is a gut microbe implicated in gastrointestinal tumorigenesis. Predicting the chemotherapeutic response is critical to developing personalised therapeutic strategies for oesophageal cancer patients. The present study investigated the relationship between F. nucleatum and chemotherapeutic resistance in oesophageal squamous cell carcinoma (ESCC).Methods We examined the relationship between F. nucleatum and chemotherapy response in 120 ESCC resected specimens and 30 pre-treatment biopsy specimens. In vitro studies using ESCC cell lines and co-culture assays further uncovered the mechanism underlying chemotherapeutic resistance.Results ESCC patients with F. nucleatum infection displayed lesser chemotherapeutic response. The infiltration and subsistence of F. nucleatum in the ESCC cells were observed by transmission electron microscopy and laser scanning confocal microscopy. We also observed that F. nucleatum modulates the endogenous LC3 and ATG7 expression, as well as autophagosome formation to induce chemoresistance against 5-FU, CDDP, and Docetaxel. ATG7 knockdown resulted in reversal of F. nucleatum-induced chemoresistance. In addition, immunohistochemical studies confirmed the correlation between F. nucleatum infection and ATG7 expression in 284 ESCC specimens.Conclusions F. nucleatum confers chemoresistance to ESCC cells by modulating autophagy. These findings suggest that targeting F. nucleatum, during chemotherapy, could result in variable therapeutic outcomes for ESCC patients.Subject terms: Tumour biomarkers, Oesophageal cancer 相似文献
63.
Philip A. Efron Tadashi Matsumoto Priscilla F. McAuliffe Philip Scumpia Ricardo Ungaro Shiro Fujita Lyle L. Moldawer David Foley Alan W. Hemming 《Journal of clinical immunology》2009,29(5):568-581
Introduction Patients undergoing major hepatectomy are at increased risk for post-operative morbidity and mortality, and changes in the
phenotype of effector cells may predispose these patients to infectious sequelae.
Methods To better understand post-hepatectomy immune responses, peripheral blood from 15 hepatectomy patients was drawn immediately
before and after liver resection and on post-operative days 1, 3, and 5. Circulating monocytes and dendritic cells were analyzed
by flow cytometry for quantity, phenotype, activation status, human leukocyte antigen DR (HLA-DR) expression, and toll-like
receptor-2 and -4 expression.
Results Major hepatectomy increased the numbers of activated CD16bright blood monocytes and the percentage of activated dendritic cells, although monocyte HLA-DR expression was reduced. These results
may represent both dysfunctional antigen presentation and pending anergy, as well as cellular priming of immune effector cells.
Better understanding of the alterations in innate immunity induced by hepatectomy may identify strategies to reduce infectious
outcomes. 相似文献
64.
Feng Xue Terumi Takahara Yutaka Yata Qiang Xia Kazunobu Nonome Eiji Shinno Masami Kanayama Shiro Takahara Toshiro Sugiyama 《Hepatology research》2008,38(8):810-817
Aim: There is growing evidence that the Rho/Rho-associated coiled coil-forming kinase (ROCK) signaling pathway is upregulated in tumors and plays a key role in cancer invasion and metastasis. Our aim was to test the anticancer effects of Rho/ROCK inhibitor, Y-27632, including possible mechanisms in a highly-metastasizing hepatocellular carcinoma (HCC) mouse model on its secretion of matrix metalloproteinase (MMP) and tumor progression.
Methods: Following orthotopic implantation of CBO140C12 HCC tumor fragments into the liver of mice, the mice were randomly assigned to a Y-27632-treated group or control group. After treatment for 4 weeks, specimens were obtained to evaluate tumor size, metastases, and immunohistochemical findings. In vitro , we examined the effects of Y-27632 and RhoC siRNA on MMP-2 and -9 expressions, invasiveness, and apoptosis in cultured tumor cells.
Results: Both RhoA and RhoC were upregulated in HCC-bearing livers, and Y-27632 significantly inhibited not only tumor growth and intrahepatic metastasis ( P < 0.05), but also tumoral MMP-9 expression. Moreover, Y-27632 treatment resulted in large necrotic areas in tumors. In vitro , Y-27632 and RhoC siRNA reduced MMP-2 and -9 expressions, as well as the chemotactic migration of tumor cells dose-dependently, and increased apoptosis eight times.
Conclusion: Y-27632 suppresses progression and limits the intrahepatic metastasis of established HCC. This could be linked to the decreased MMP expression and induction of apoptosis in tumor cells. Rho signaling may prove to be a productive target in anticancer therapy. 相似文献
Methods: Following orthotopic implantation of CBO140C12 HCC tumor fragments into the liver of mice, the mice were randomly assigned to a Y-27632-treated group or control group. After treatment for 4 weeks, specimens were obtained to evaluate tumor size, metastases, and immunohistochemical findings. In vitro , we examined the effects of Y-27632 and RhoC siRNA on MMP-2 and -9 expressions, invasiveness, and apoptosis in cultured tumor cells.
Results: Both RhoA and RhoC were upregulated in HCC-bearing livers, and Y-27632 significantly inhibited not only tumor growth and intrahepatic metastasis ( P < 0.05), but also tumoral MMP-9 expression. Moreover, Y-27632 treatment resulted in large necrotic areas in tumors. In vitro , Y-27632 and RhoC siRNA reduced MMP-2 and -9 expressions, as well as the chemotactic migration of tumor cells dose-dependently, and increased apoptosis eight times.
Conclusion: Y-27632 suppresses progression and limits the intrahepatic metastasis of established HCC. This could be linked to the decreased MMP expression and induction of apoptosis in tumor cells. Rho signaling may prove to be a productive target in anticancer therapy. 相似文献
65.
Yano A Tsutsumi S Soga S Lee MJ Trepel J Osada H Neckers L 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(40):15541-15546
Hsp90 inhibitors are being evaluated extensively in patients with advanced cancers. However, the impact of Hsp90 inhibition on signaling pathways in normal tissues and the effect that this may have on the antitumor activity of these molecularly targeted drugs have not been rigorously examined. Breast and prostate carcinomas are among those cancers that respond to Hsp90 inhibitors in animal xenograft models and in early studies in patients. Because these cancers frequently metastasize to bone, it is important to determine the impact of Hsp90 inhibitors in the bone environment. In the current study, we show that, in contrast to its activity against prostate cancer cells in vitro and its inhibition of s.c. prostate cancer xenografts, the Hsp90 inhibitor 17-AAG stimulates the intraosseous growth of PC-3M prostate carcinoma cells. This activity is mediated not by a direct effect on the tumor but by Hsp90-dependent stimulation of osteoclast maturation. Hsp90 inhibition transiently activates osteoclast Src kinase and promotes Src-dependent Akt activation. Both kinases are key drivers of osteoclast maturation, and three agents that block osteoclastogenesis, the Src inhibitor dasatinib, the bisphosphonate alendronate, and the osteoclast-specific apoptosis-inducer reveromycin A, markedly reduced 17-AAG-stimulated tumor growth in bone. These data emphasize the importance of understanding the complex role played by Hsp90 in regulating signal transduction pathways in normal tissues as well as in cancer cells, and they demonstrate that drug-dependent modulation of the local tumor environment may profoundly affect the antitumor efficacy of Hsp90-directed therapy. 相似文献
66.
Kihara Mari Sugihara Takahiko Asano Junichi Sato Midori Kaneko Hiroshi Muraoka Sei Ohshima Shiro Nanki Toshihiro 《Clinical rheumatology》2022,41(12):3661-3673
Clinical Rheumatology - To describe clinical characteristics of patients in Japan with coronavirus disease 19 (COVID-19) and pre-existing rheumatic disease and examine the possible risk factors... 相似文献
67.
Augmented platelet reactivity and thromboxane A2 production possible aggravating factors in unstable angina 总被引:2,自引:0,他引:2
We examined platelet aggregation and plasma levels of thromboxane B2, a stable metabolite of thromboxane A2, in patients with unstable angina and correlated these platelet indices with the response to antianginal conventional therapy such as isosorbide dinitrate and calcium channel blocker. Eight of 36 patients exhibited anginal attacks more than 5 times/week in spite of the therapy, designated refractory unstable angina, associated with augmented platelet aggregation induced by arachidonate (0.3 mM, 71 +/- 3%, mean +/- SEM) and collagen (2 micrograms/ml, 72 +/- 5%), and elevated plasma levels of thromboxane B2 (350 +/- 19 pg/ml). In the remainder of the patients whose anginal attacks were effectively subsided by the therapy, platelet aggregation was much lower (arachidonate: 34 +/- 9%, collagen: 31 +/- 8%, p less than 0.01) and plasma levels of thromboxane B2 were also lower (295 +/- 12 pg/ml, p less than 0.05). To evaluate the effect of selective thromboxane A2 blockade on clinical findings and platelet reactivity in refractory unstable angina, OKY-046 (600 mg/day, p.o.) was administered to another 14 patients with refractory unstable angina in addition to the conventional therapy. We found that platelet aggregation induced by arachidonate (71 +/- 4%) and collagen 65 +/- 8%) was markedly reduced (44 +/- 7% and 24 +/- 3%, respectively, p less than 0.01) and plasma levels of thromboxane B2 (358 +/- 31 pg/ml) and thromboxane B2 production in serum (29 +/- 5 ng/ml) were also significantly reduced after OKY-046 treatment (262 +/- 21 pg/ml, p less than 0.05, and 1.4 +/- 0.2 ng/ml, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
68.
Maki Akasu M.D. Keijiro Saku M.D. Masanori Okabe M.D. Koichi Handa M.D. Kunihiro Matsuo M.D. Shiro Jimi Ph.D. Kikuo Arakawa M.D. 《The International journal of angiology》1995,4(3):169-171
Typical angioid streaks were found on routine ophthalmologic examination in a 42-year-old female with yellowish, coalescing papules on her neck without any symptoms. Biopsy of the cutaneous lesion showed degeneration and fragmentation of the elastic fibers and many basophilic-stained calcifications in mid-dermis, which are consistent with pseudoxanthoma elasticum. Twenty-four-hour Holter electrocardiography (ECG) showed sinus arrest for 2.5 seconds, and an electrophysiological study revealed sinus nodal dysfunction (sick sinus syndrome), whereas all of the coronary arteries were intact, despite a treadmill stress ECG test showing significant ST depressions. The association of pseudoxanthoma elasticum and sick sinus syndrome is very rare. One possible explanation for this association here is that the degeneration of elastic fiber in endomysium of the sino-atrial node may have affected heart conduction systems, resulting in sick sinus syndrome.Part of this work was presented at the 76th Japanese Circulation Society Kyushu Meeting, Japan, June 18, 1994 相似文献
69.
Shingen Nakamura Momoyo Azuma Tomoko Maruhashi Kimiko Sogabe Ryohei Sumitani Munenori Uemura Masami Iwasa Shiro Fujii Hirokazu Miki Kumiko Kagawa Takashi Hiraga Noriyasu Kondo Hiromi Fujita Fumihiko Mahara Masahiro Abe 《Journal of infection and chemotherapy》2018,24(5):389-392
Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). Clinical symptoms of SFTS often involve encephalopathy and other central neurological symptoms, particularly in seriously ill patients; however, pathogenesis of encephalopathy by SFTSV is largely unknown. Herein, we present case reports of three patients with SFTS, complicated by encephalopathy, admitted to Tokushima University hospital: one patient was a 63-year-old man, while the other two were 83- and 86-year-old women. All of them developed disturbance of consciousness around the 7th day post onset of fever. After methylprednisolone pulse therapy of 500 mg/day, all of them recovered without any neurological sequelae. SFTSV genome was not detected in the cerebrospinal fluid of 2 out of the 3 patients that were available for examination. In these patients, disturbance of consciousness seemed to be an indirect effect of the cytokine storm triggered by SFTSV infection. We propose that short-term glucocorticoid therapy might be beneficial in the treatment of encephalopathy during early phase of SFTSV infection. 相似文献
70.
Mutsumi Matsuu-Matsuyama Kazuko Shichijo Kumio Okaichi Tomomi Kurashige Hisayoshi Kondo Shiro Miura Masahiro Nakashima 《Journal of radiation research》2015,56(3):493-501
Exposure to ionizing radiation during childhood is a well-known risk factor for thyroid cancer. Our study evaluated the effect of age on the radiosensitivity of rat thyroid glands. Four-week-old (4W), 7 -week-old (7W), and 8-month-old (8M) male Wistar rats were exposed to 8 Gy of whole-body X-ray irradiation. Thyroids were removed 3–72 h after irradiation, and non-irradiated thyroids served as controls. Ki67-positivity and p53 binding protein 1 (53BP1) focus formation (a DNA damage response) were evaluated via immunohistochemistry. Amounts of proteins involved in DNA damage response (p53, p53 phosphorylated at serine 15, p21), apoptosis (cleaved caspase-3), and autophagy (LC3, p62) were determined via western blotting. mRNA levels of 84 key autophagy-related genes were quantified using polymerase chain reaction arrays. Ki67-positive cells in 4W (with high proliferative activity) and 7W thyroids significantly decreased in number post-irradiation. The number of 53BP1 foci and amount of p53 phosphorylated at serine 15 increased 3 h after irradiation, regardless of age. No increase in apoptosis or in the levels of p53, p21 or cleaved caspase-3 was detected for any ages. Levels of LC3-II and p62 increased in irradiated 4W but not 8M thyroids, whereas expression of several autophagy-related genes was higher in 4W than 8M irradiated thyroids. Irradiation increased the expression of genes encoding pro-apoptotic proteins in both 4W and 8M thyroids. In summary, no apoptosis or p53 accumulation was noted, despite the expression of some pro-apoptotic genes in immature and adult thyroids. Irradiation induced autophagy in immature, but not in adult, rat thyroids. 相似文献