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排序方式: 共有314条查询结果,搜索用时 640 毫秒
1.
Mice lacking smooth muscle calponin display increased bone formation that is associated with enhancement of bone morphogenetic protein responses 总被引:5,自引:0,他引:5
2.
Nagai Y Fujikake N Ohno K Higashiyama H Popiel HA Rahadian J Yamaguchi M Strittmatter WJ Burke JR Toda T 《Human molecular genetics》2003,12(11):1253-1259
Polyglutamine (polyQ) diseases are a growing class of inherited neurodegenerative diseases including Huntington's disease, which are caused by abnormal expansions of the polyQ stretch in each unrelated disease protein. The expanded polyQ stretch is thought to confer toxic properties on the disease proteins through alteration of their conformation leading to pathogenic protein-protein interactions including oligomerization and/or aggregation. Hypothesizing that molecules with selective binding affinity to the expanded polyQ stretch may interfere with the pathogenic properties, we previously identified Polyglutamine Binding Peptide 1 (QBP1) from combinatorial peptide phage display libraries. We show here that a tandem repeat of the inhibitor peptide QBP1, (QBP1)(2), significantly suppresses polyQ aggregation and polyQ-induced neurodegeneration in the compound eye of Drosophila polyQ disease models, which express the expanded polyQ protein under the eye specific promoter. Most importantly, (QBP1)(2) expression dramatically rescues premature death of flies expressing the expanded polyQ protein in the nervous system, resulting in the dramatic increase of the median life span from 5.5 to 52 days. These results suggest that QBP1 can prevent polyQ-induced neurodegeneration in vivo. We propose that QBP1 prevents polyQ oligomerization and/or aggregation either by altering the toxic conformation of the expanded polyQ stretch, or by simply competing with the expanded polyQ stretches for binding to other expanded polyQ proteins. The peptide inhibitor QBP1 is a promising candidate with great potential as a therapeutic molecule against the currently untreatable polyQ diseases. 相似文献
3.
Takashi Kuribayashi Tetsuro Seita Katsuhito Kawato Shunsuke Yamazaki Shizuo Yamamoto 《Inflammation》2013,36(6):1448-1452
Synthesis of α2-macoglobulin (α2M) by 3-week-old juvenile rats was compared to that of mature 7- and 11-week-old rats. Serum concentrations of α2M, interleukin (IL)-6- and cytokine-induced neutrophil chemoattractant (CINC)-1 were measured by enzyme-linked immunosorbent assay. The area under the concentration vs. time curve (AUC) for α2M was significantly different among the three groups. The synthesis of α2M increased in an age-dependent manner. No significant difference was observed for the AUC of IL-6, but that of CINC-1 in 3-week-old rats was significantly lower than that in 7- or 11-week-old rats. These results suggest that synthesis of α2M was increased in mature compared to juvenile rats, possibly due to differences in liver function. The maximum concentration of CINC-1 in 3-week-old rats was observed 6 h after turpentine oil injection. The serum concentrations of IL-6 and CINC-1 increased more quickly in juvenile rats than in mature rats after inflammatory stimulation. 相似文献
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Shota Hamada Shiro Hinotsu Katsuhito Hori Hiroshi Furuse Takehiro Oikawa Junichi Kawakami Seiichiro Ozono Hideyuki Akaza Koji Kawakami 《Supportive care in cancer》2012,20(4):813-820
Purpose
The objective of this study was to estimate the cost of antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in daily practice in Japan. 相似文献6.
Whole‐exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene
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C. Christofer Juhlin Adam Stenman Felix Haglund Victoria E. Clark Taylor C. Brown Jacob Baranoski Kaya Bilguvar Gerald Goh Jenny Welander Fredrika Svahn Jill C. Rubinstein Stefano Caramuta Katsuhito Yasuno Murat Günel Martin Bäckdahl Oliver Gimm Peter Söderkvist Manju L. Prasad Reju Korah Richard P. Lifton Tobias Carling 《Genes, chromosomes & cancer》2015,54(9):542-554
As subsets of pheochromocytomas (PCCs) lack a defined molecular etiology, we sought to characterize the mutational landscape of PCCs to identify novel gene candidates involved in disease development. A discovery cohort of 15 PCCs wild type for mutations in PCC susceptibility genes underwent whole‐exome sequencing, and an additional 83 PCCs served as a verification cohort for targeted sequencing of candidate mutations. A low rate of nonsilent single nucleotide variants (SNVs) was detected (6.1/sample). Somatic HRAS and EPAS1 mutations were observed in one case each, whereas the remaining 13 cases did not exhibit variants in established PCC genes. SNVs aggregated in apoptosis‐related pathways, and mutations in COSMIC genes not previously reported in PCCs included ZAN, MITF, WDTC1, and CAMTA1. Two somatic mutations and one constitutional variant in the well‐established cancer gene lysine (K)‐specific methyltransferase 2D (KMT2D, MLL2) were discovered in one sample each, prompting KMT2D screening using focused exome‐sequencing in the verification cohort. An additional 11 PCCs displayed KMT2D variants, of which two were recurrent. In total, missense KMT2D variants were found in 14 (11 somatic, two constitutional, one undetermined) of 99 PCCs (14%). Five cases displayed somatic mutations in the functional FYR/SET domains of KMT2D, constituting 36% of all KMT2D‐mutated PCCs. KMT2D expression was upregulated in PCCs compared to normal adrenals, and KMT2D overexpression positively affected cell migration in a PCC cell line. We conclude that KMT2D represents a recurrently mutated gene with potential implication for PCC development. © 2015 The Authors. Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc. 相似文献
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9.
Katsuhito Nagano 《Journal of Physical Therapy Science》2015,27(11):3585-3591
[Purpose] The purpose of this study was to elucidate the cathepsin-D involvement in
signaling pathways for the survival and apoptosis of myofibers in rats with
hindlimb-unloading in a low-temperature environment. [Subjects and Methods] Wistar rats
were divided into two groups: a control group and a group that underwent hindlimb
unloading in a low-temperature environment to induce muscle apoptosis. Cathepsin-D
localization in the soleus and extensor digitorum longus muscles, along with the
expression of cathepsin-D in apoptotic myofibers, was examined. Expression of the active
and inactive forms of cathepsin-D was also analyzed. [Results] Cathepsin-D was mainly
expressed in type I myofibers and was observed to have punctate patterns in the control
group. In the hindlimb unloading in a low-temperature environment group, the type I
myofiber composition ratio decreased, and caspase-3 activation and TUNEL-positive
apoptotic myofibers were observed. In caspase-3-activated myofibers, cathepsin-D
overexpression and leakage of it into the cytoplasm were observed. In the hindlimb
unloading in a low-temperature environment group, the amount of inactive cathepsin-D
decreased, whereas that of the active form increased. [Conclusion] Cathepsin-D was deduced
to be indicative of a myofiber-type classification and a factor related to myofiber type
maintenance. In addition, cathepsin-D leakage into the cytoplasm was appeared to be
involved in caspase-3 activation in the hindlimb unloading in a low-temperature
environment group.Key words: Cathepsin-D, Apoptosis, Muscle fiber type 相似文献
10.
The laparoscopic technique for repairing ventral and incisional hernias (VIH) is now well established. However, several issues related to laparoscopic VIH repair, such as the high recurrence rate for hernias with large fascial defects and in extremely obese patients, are yet to be resolved. Additional problems include seroma formation, mesh bulging/eventration, and non-restoration of the abdominal wall rigidity/function with only bridging of the hernial orifice using standard laparoscopic intraperitoneal onlay mesh repair (sIPOM). To solve these problems, laparoscopic fascial defect closure with IPOM reinforcement (IPOM-Plus) has been introduced in the past decade, and a few studies have reported satisfactory outcomes. Although detailed techniques for fascial defect closure and handling of the mesh have been published, standardized techniques are yet to be established. We reviewed the literature on IPOM-Plus in the PubMed database and identified 16 reports in which the recurrence rate, incidence of seroma formation, and incidence of mesh bulging were 0–7.7, 0–11.4, and 0 %, respectively. Several comparison studies between sIPOM and IPOM-Plus seem to suggest that IPOM-Plus is associated with more favorable surgical outcomes; however, larger-scale studies are essential. 相似文献