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排序方式: 共有316条查询结果,搜索用时 31 毫秒
111.
Makoto Takahashi Masato Obayashi Taro Ishiguro Nozomu Sato Yusuke Niimi Kokoro Ozaki Kaoru Mogushi Yasen Mahmut Hiroshi Tanaka Fuminori Tsuruta Ricardo Dolmetsch Mitsunori Yamada Hitoshi Takahashi Takeo Kato Osamu Mori Yoshinobu Eishi Hidehiro Mizusawa Kinya Ishikawa 《PloS one》2013,8(3)
The human α1A voltage-dependent calcium channel (Cav2.1) is a pore-forming essential subunit embedded in the plasma membrane. Its cytoplasmic carboxyl(C)-tail contains a small poly-glutamine (Q) tract, whose length is normally 4∼19 Q, but when expanded up to 20∼33Q, the tract causes an autosomal-dominant neurodegenerative disorder, spinocerebellar ataxia type 6 (SCA6). A recent study has shown that a 75-kDa C-terminal fragment (CTF) containing the polyQ tract remains soluble in normal brains, but becomes insoluble mainly in the cytoplasm with additional localization to the nuclei of human SCA6 Purkinje cells. However, the mechanism by which the CTF aggregation leads to neurodegeneration is completely elusive, particularly whether the CTF exerts more toxicity in the nucleus or in the cytoplasm. We tagged recombinant (r)CTF with either nuclear-localization or nuclear-export signal, created doxycyclin-inducible rat pheochromocytoma (PC12) cell lines, and found that the CTF is more toxic in the cytoplasm than in the nucleus, the observations being more obvious with Q28 (disease range) than with Q13 (normal-length). Surprisingly, the CTF aggregates co-localized both with cAMP response element-binding protein (CREB) and phosphorylated-CREB (p-CREB) in the cytoplasm, and Western blot analysis showed that the quantity of CREB and p-CREB were both decreased in the nucleus when the rCTF formed aggregates in the cytoplasm. In human brains, polyQ aggregates also co-localized with CREB in the cytoplasm of SCA6 Purkinje cells, but not in other conditions. Collectively, the cytoplasmic Cav2.1-CTF aggregates are sufficient to cause cell death, and one of the pathogenic mechanisms may be abnormal CREB trafficking in the cytoplasm and reduced CREB and p-CREB levels in the nuclei. 相似文献
112.
Maki Ohsawa Toshiyuki Kobayashi Hidehiro Okura Takashi Igarashi Masashi Mizuguchi Okio Hino 《PloS one》2013,8(1)
The tumor-suppressor genes TSC1 and TSC2 are mutated in tuberous sclerosis, an autosomal dominant multisystem disorder. The gene products of TSC1 and TSC2 form a protein complex that inhibits the signaling of the mammalian target of rapamycin complex1 (mTORC1) pathway. mTORC1 is a crucial molecule in the regulation of cell growth, proliferation and survival. When the TSC1/TSC2 complex is not functional, uncontrolled mTORC1 activity accelerates the cell cycle and triggers tumorigenesis. Recent studies have suggested that TSC1 and TSC2 also regulate the activities of Rac1 and Rho, members of the Rho family of small GTPases, and thereby influence the ensuing actin cytoskeletal organization at focal adhesions. However, how TSC1 contributes to the establishment of cell polarity is not well understood. Here, the relationship between TSC1 and the formation of the actin cytoskeleton was analyzed in stable TSC1-expressing cell lines originally established from a Tsc1-deficient mouse renal tumor cell line. Our analyses showed that cell proliferation and migration were suppressed when TSC1 was expressed. Rac1 activity in these cells was also decreased as was formation of lamellipodia and filopodia. Furthermore, the number of basal actin stress fibers was reduced; by contrast, apical actin fibers, originating at the level of the tight junction formed a network in TSC1-expressing cells. Treatment with Rho-kinase (ROCK) inhibitor diminished the number of apical actin fibers, but rapamycin had no effect. Thus, the actin fibers were regulated by the Rho-ROCK pathway independently of mTOR. In addition, apical actin fibers appeared in TSC1-deficient cells after inhibition of Rac1 activity. These results suggest that TSC1 regulates cell polarity-associated formation of actin fibers through the spatial regulation of Rho family of small GTPases. 相似文献
113.
Seong-Won Nho Jun-ichi Hikima Seong Bin Park Ho Bin Jang In Seok Cha Motoshige Yasuike Yoji Nakamura Atsushi Fujiwara Motohiko Sano Kinya Kanai Hidehiro Kondo Ikuo Hirono Haruko Takeyama Takashi Aoki Tae-Sung Jung 《PloS one》2013,8(11)
Streptococcus parauberis, which is the main causative agent of streptococcosis among olive flounder (Paralichthys olivaceus) in northeast Asia, can be distinctly divided into two groups (type I and type II) by an agglutination test. Here, the whole genome sequences of two Japanese strains (KRS-02083 and KRS-02109) were determined and compared with the previously determined genome of a Korean strain (KCTC 11537). The genomes of S. parauberis are intermediate in size and have lower GC contents than those of other streptococci. We annotated 2,236 and 2,048 genes in KRS-02083 and KRS-02109, respectively. Our results revealed that the three S. parauberis strains contain different genomic insertions and deletions. In particular, the genomes of Korean and Japanese strains encode different factors for sugar utilization; the former encodes the phosphotransferase system (PTS) for sorbose, whereas the latter encodes proteins for lactose hydrolysis, respectively. And the KRS-02109 strain, specifically, was the type II strain found to be able to resist phage infection through the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system and which might contribute valuably to serologically distribution. Thus, our genome-wide association study shows that polymorphisms can affect pathogen responses, providing insight into biological/biochemical pathways and phylogenetic diversity. 相似文献
114.
Dowell JD Tsai SC Dias-Santagata DC Nakajima H Wang Z Zhu W Field LJ 《Biochimica et biophysica acta》2007,1773(3):358-366
p193/CUL7 is an E3 ubiquitin ligase initially identified as an SV40 Large T Antigen binding protein. Expression of a dominant interfering variant of mouse p193/CUL7 (designated 1152stop) conferred resistance to MG132- and etoposide-induced apoptosis in U2OS cells. Immune precipitation/Western analyses revealed that endogenous p193/CUL7 formed a complex with Parc (a recently identified parkin-like ubiquitin ligase) and p53. Apoptosis resistance did not result from 1152stop-mediated disruption of the endogenous p193/CUL7 binding partners. Moreover, 1152stop molecule did not directly bind to endogenous p193/CUL7, Parc or p53. These data suggested a role for p193/CUL7 in the regulation of apoptosis independently of p53 and Parc activity. 相似文献
115.
OBJECTIVE: To compare the cytologic findings and diagnoses of breast fine needle aspiration (FNA) samples of well-defined lesions (WDL) with those of poorly defined indurated lesions. STUDY DESIGN: We examined 371 consecutive breast FNA specimens obtained without diagnostic image guidance. Fifty-eight lesions were described by the examining pathologists as PDILs, and the remaining 313 lesions were described as WDLs. RESULTS: Compared with WDLs, PDILs were more likely to yield hypocellular specimens deemed unsatisfactory for diagnostic evaluation (37.9% vs. 14.1%). However, a substantial number of atypical, suspicious for malignancy and malignant cases (12.1%, 5.2%, and 13.8%, respectively) were identified with PDILs. In addition, benign diagnoses were more frequently rendered with aspirates of WDLs, compared with PDILs (47.9% vs. 31.0%). In our study, FNAs of PDILs were more often diagnostic in white women < 49 years of age and in lesions measuring > 2 cm. CONCLUSION: Given the relatively high frequency of malignant, suspicious and atypical lesions detected with PDILs, FNA is a suitable first diagnostic approach for PDILs, especially considering the relatively low cost and simplicity of FNA procedures without diagnostic imaging guidance. 相似文献
116.
BACKGROUND: Carcinoma metastatic to the pituitary gland is infrequent and has been reportedly detected in approximately 1% of pituitary surgical cases. It may masquerade as a pituitary adenoma both clinically and radiologically. CASE: A 49-year-old man presented with a 1-month history of severe headache, diplopia and blurred vision. Neurologic examination revealed bitemporal hemianopsia and left sixth nerve palsy. The initial radiologic diagnosis based on magnetic resonance imaging was pituitary adenoma. A biopsy of the lesion was performed. While intraoperative frozen section examination could not completely exclude an "atypical" pituitary adenoma, cytologic touch imprint findings were diagnostic of metastatic small cell carcinoma. Subsequently, additional workup revealed that the patient had a mass lesion in the right lung and right-sided mediastinal lymphadenopathy on chest computed tomography. This was a rare case of pituitary metastasis as the first manifestation of an occult malignancy. CONCLUSION: For intraoperative diagnosis at the time ofpituitary surgery, cytologic imprints can be used reliably to make a diagnosis not only of pituitary adenoma but also of metastatic lesions. It is appropriate in current neuropathology practice that the imprint method be used as the sole modality for intraoperative consultation for pituitary lesions. 相似文献
117.
Characterization of Japanese flounder (Paralichthys olivaceus) NK-lysin, an antimicrobial peptide 总被引:1,自引:0,他引:1
Hirono I Kondo H Koyama T Arma NR Hwang JY Nozaki R Midorikawa N Aoki T 《Fish & shellfish immunology》2007,22(5):567-575
The NK-lysin cDNA of Japanese flounder, Paralichthys olivaceus, consists of 657bp, containing an open reading frame (ORF) of 444bp, which encodes 147 amino acid residues. The amino acid sequence of Japanese flounder NK-lysin has 21% identity to porcine NK-lysin and bovine NK-lysin, 23% to equine NK-lysin, and 46% to zebrafish NK-lysin-like protein. Multiple alignments of Japanese flounder NK-lysin and other known saposin-like proteins revealed that the six cysteine residues important for structural folding are completely conserved. The Japanese flounder NK-lysin gene is approximately 2kb and consists of five exons and four introns. Japanese flounder NK-lysin mRNA constitutive expression was mainly detected in gills, heart, head kidney, intestines, peripheral blood leukocytes (PBLs), spleen and trunk kidney, and was detected at low levels in liver, muscle and ovary. However, expression was not detected in brain, skin and stomach of apparently healthy Japanese flounder. Gene expression of Japanese flounder NK-lysin was not inducible by lipopolysaccharide (LPS) treatment. A synthesized NK-lysin peptide, consisting of 27 amino acid residues, showed antimicrobial activity against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Photobacterium damselae subsp. piscicida. 相似文献
118.
Hidehiro Nakamura Sachise KarakawaAkiko Watanabe Yasuko KawamataTomomi Kuwahara Kazutaka ShimboRyosei Sakai 《Analytical biochemistry》2015
6-Aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) is an amino acid-specific derivatizing reagent that has been used for sensitive amino acid quantification by liquid chromatography–tandem quadrupole mass spectrometry (LC–MS/MS). In this study, we aimed to evaluate the ability of this method to measure the isotopic enrichment of amino acids and to determine the positional 15N enrichment of urea cycle amino acids (i.e., arginine, ornithine, and citrulline) and glutamine. The distribution of the M and M + 1 isotopomers of each natural AQC–amino acid was nearly identical to the theoretical distribution. The standard deviation of the (M + 1)/M ratio for each amino acid in repeated measurements was approximately 0.1%, and the ratios were stable regardless of the injected amounts. Linearity in the measurements of 15N enrichment was confirmed by measuring a series of 15N-labeled arginine standards. The positional 15N enrichment of urea cycle amino acids and glutamine was estimated from the isotopic distribution of unique fragment ions generated at different collision energies. This method was able to identify their positional 15N enrichment in the plasma of rats fed 15N-labeled glutamine. These results suggest the utility of LC–MS/MS detection of AQC–amino acids for the measurement of isotopic enrichment in 15N-labeled amino acids and indicate that this method is useful for the study of nitrogen metabolism in living organisms. 相似文献
119.
Masaki Watanabe Yoshiro Suzuki Kunitoshi Uchida Naoyuki Miyazaki Kazuyoshi Murata Seiji Matsumoto Hidehiro Kakizaki Makoto Tominaga 《The Journal of biological chemistry》2015,290(50):29882-29892
Trpm7 is a divalent cation-permeable channel that has been reported to be involved in magnesium homeostasis as well as cellular adhesion and migration. We generated urothelium-specific Trpm7 knock-out (KO) mice to reveal the function of Trpm7 in vivo. A Trpm7 KO was induced by tamoxifen and was confirmed by genomic PCR and immunohistochemistry. By using patch clamp recordings in primary urothelial cells, we observed that Mg2+-inhibitable cation currents as well as acid-inducible currents were significantly smaller in Trpm7 KO urothelial cells than in cells from control mice. Assessment of voiding behavior indicated a significantly smaller voided volume in Trpm7 KO mice (mean voided volume 0.28 ± 0.08 g in KO mice and 0.36 ± 0.04 g in control mice, p < 0.05, n = 6–8). Histological analysis showed partial but substantial edema in the submucosal layer of Trpm7 KO mice, most likely due to inflammation. The expression of proinflammatory cytokines TNF-α and IL-1β was significantly higher in Trpm7 KO bladders than in controls. In transmission electron microscopic analysis, immature intercellular junctions were observed in Trpm7 KO urothelium but not in control mice. These results suggest that Trpm7 is involved in the formation of intercellular junctions in mouse urothelium. Immature intercellular junctions in Trpm7 knock-out mice might lead to a disruption of barrier function resulting in inflammation and hypersensitive bladder afferent nerves that may affect voiding behavior in vivo. 相似文献
120.