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排序方式: 共有590条查询结果,搜索用时 703 毫秒
71.
Nathan D. Mathewson Orr Ashenberg Itay Tirosh Simon Gritsch Elizabeth M. Perez Sascha Marx Livnat Jerby-Arnon Rony Chanoch-Myers Toshiro Hara Alyssa R. Richman Yoshinaga Ito Jason Pyrdol Mirco Friedrich Kathrin Schumann Michael J. Poitras Prafulla C. Gokhale L. Nicolas Gonzalez Castro Marni E. Shore Kai W. Wucherpfennig 《Cell》2021,184(5):1281-1298.e26
72.
Helga E. Hildebrandt-Stark George J. Marcus Koji Yoshinaga Harold R. Behrman Roy O. Greep 《Prostaglandins & other lipid mediators》1975,9(2):231-244
Adult female guinea pigs were actively immunized with prostaglandin F2α conjugated to bovine serum albumin (BSA). Control animals, immunized against BSA continued to cycle normally, while the animals immunized against prostaglandin F2α stopped cycling after one to three normal cycles. Laparotomy at 30 days after the last estrus revealed no recently formed corpora lutea. During the remaining 70 days of observation the antibody titer increased to 1:700, accompanied by increasing total serum estrogens (136 pg/ml at day 100) and a slow decline in circulating progesterone levels (0.6 ng/ml at day 100). The ovaries at day 100 contained degenerated corpora lutea and luteinized follicles. The suppression of the estrous cycle in the present experiments was interpreted as resulting from prolongation of luteal function as well as from inhibition of ovulation. 相似文献
73.
Naoki Tokuhara Kana Namiki Mai Uesugi Chihiro Miyamoto Makoto Ohgoh Katsutoshi Ido Takashi Yoshinaga Toshihiko Yamauchi Junro Kuromitsu Sadao Kimura Norimasa Miyamoto Yoshitoshi Kasuya 《The Journal of biological chemistry》2010,285(43):33294-33306
One of the family of voltage-gated calcium channels (VGCC), the N-type Ca2+ channel, is located predominantly in neurons and is associated with a variety of neuronal responses, including neurodegeneration. A precise mechanism for how the N-type Ca2+ channel plays a role in neurodegenerative disease, however, is unknown. In this study, we immunized N-type Ca2+ channel α1B-deficient (α1B−/−) mice and their wild type (WT) littermates with myelin oligodendrocyte glycoprotein 35–55 and analyzed the progression of experimental autoimmune encephalomyelitis (EAE). The neurological symptoms of EAE in the α1B−/− mice were less severe than in the WT mice. In conjunction with these results, sections of the spinal cord (SC) from α1B−/− mice revealed a reduction in both leukocytic infiltration and demyelination compared with WT mice. No differences were observed in the delayed-type hypersensitivity response, spleen cell proliferation, or cytokine production from splenocytes between the two genotypes. On the other hand, Western blot array analysis and RT-PCR revealed that a typical increase in the expression of MCP-1 in the SC showed a good correlation with the infiltration of leukocytes into the SC. Likewise, immunohistochemical analysis showed that the predominant source of MCP-1 was activated microglia. The cytokine-induced production of MCP-1 in primary cultured microglia from WT mice was significantly higher than that from α1B−/− mice and was significantly inhibited by a selective N-type Ca2+ channel antagonist, ω-conotoxin GVIA or a withdrawal of extracellular Ca2+. These results suggest that the N-type Ca2+ channel is involved in the pathogenesis of EAE at least in part by regulating MCP-1 production by microglia. 相似文献
74.
75.
Yuki Kanase Takafumi Kitada Hidetsugu Tabata Kosho Makino Tetsuta Oshitari Hiromi Ohashi Takashi Yoshinaga Hideaki Natsugari Hideyo Takahashi 《Bioorganic & medicinal chemistry》2018,26(9):2508-2513
The physicochemical properties of 4-substituted carbamazepine derivatives were investigated. It was elucidated that the 4-substitution is not effective in reducing the rotations (E/Z) about the N—C1′ axes around the outer carbamoyl moiety. However, the atropisomers were isolated with high stereochemical stability, meaning that the 4-substitution reduced the butterfly motion of the tricyclic ring system efficiently. The Cl/CH3-substituted carbamazepine derivatives showed greater inhibitory effects on hNav1.2 channel currents compared with carbamazepine, although no difference in the activity between enantiomers was observed. 相似文献
76.
M. Nakai Kiyotaka Toshimori Kazuya Yoshinaga Tetsuo Nasu Rex A. Hess 《Cell and tissue research》1998,294(1):145-152
Effects of a single, high dose of orally administered carbendazim (100 mg/kg) on acrosome formation in the early phases of
spermiogenesis were examined by electron microscopy and immunocytochemistry up to day 7.5 post-treatment. No obvious abnormality
of acrosome development was noted in the Golgi phase spermatids on day 1.5 post-treatment. On day 3, step 1 spermatids were
seen in stage III seminiferous tubules. In stage V tubules at this post-treatment interval, direct connections between the
trans-side saccules of the Golgi stacks and the outer acrosomic membranes were observed in step 5 spermatids. Similar direct
connections between these two organelles were also observed in the advanced round spermatids in later stages at days 4.5 and
7.5. On day 4.5, step 1 and 3 spermatids were seen in stage V tubules. On day 7.5, round spermatids with various abnormalities
of acrosome development were observed in stage VII tubules, in addition to the discontinuous and granular acrosomes reported
previously. These features were not observed in testes of control animals. In the immunocytochemical analysis using an antibody
mMN7 that recognizes a protein delivered from the Golgi apparatus to the acrosome, spermatids exposed to carbendazim showed
various abnormal immunostaining patterns in the acrosomes. On the other hand, strong immunoreactivity was observed in the
Golgi saccules connecting to the acrosomes. These results suggest that in testis treated with carbendazim acrosome development
is impaired during the early phases of spermiogenesis, and material supply from the Golgi apparatus to the acrosome is perturbed,
which is a possible cause of the abnormal development.
Received: 31 March 1998 / Accepted: 28 May 1998 相似文献
77.
Glutathione transferases (GSTs) are multifunctional enzymes found in many organisms. We recently identified vanadium-binding GSTs, designated AsGSTs, from the vanadium-rich ascidian, Ascidia sydneiensis samea. In this study, the metal-selectivity of AsGST-I was investigated. Immobilized metal ion affinity chromatography (IMAC) analysis revealed that AsGST-I binds to V(IV), Fe(III), and Cu(II) with high affinity in the following order Cu(II)>V(IV)>Fe(III), and to Co(II), Ni(II), and Zn(II) with low affinity. The GST activity of AsGST-I was inhibited dose-dependently by not V(IV) but Cu(II). A competition experiment demonstrated that the binding of V(IV) to AsGST-I was not inhibited by Cu(II). These results suggest that AsGST-I has high V(IV)-selectivity, which can confer the specific vanadium accumulation of ascidians. Because there are few reports on the metal-binding ability of GSTs, we performed the same analysis on SjGST (GST from the schistosome, Schistosoma japonicum). SjGST also demonstrated metal-binding ability although the binding pattern differed from that of AsGST-I. The GST activity of SjGST was inhibited by Cu(II) only, as that of AsGST-I. Our results indicate a possibility that metal-binding abilities of GSTs are conserved among organisms, at least animals, which is suggestive of a new role for these enzymes in metal homeostasis or detoxification. 相似文献
78.
In cardiac myocytes, the effect of alpha1-adrenergic stimulation on L-type Ca current remains to be clarified. We examined this issue by the transient coexpression of alpha1-adrenoceptors on BHKC12 cells, where recombinant Ca channels composed of cardiac alpha1 subunit and skeletal beta, gamma, alpha2/delta subunits were stably expressed. After transfection of plasmid DNA encoding bovine alpha1C-adrenoceptors, bath-applied phenylephrine potentiated the cloned Ca channel current during perforated-patch whole-cell recording by 26+/-6% in 6 out of 12 cells. The potentiation was elicited also by methoxamine, and was blocked by prazosin. Phenylephrine also increased the channel open probability during cell-attached single channel recording in 7 out of 15 cells. The ratio of successful modulation of Ca channels was in accordance with the ratio of successful expression of alpha1-adrenoceptors, as estimated by beta-galactosidase staining. These results suggest that the stimulation of alpha1C-adrenoceptors is linked to potentiation of cardiac L-type Ca current. BHK cells provide a valuable expression system to study the modulation of Ca channels evoked by a receptor stimulation. 相似文献
79.
80.
Hidefumi Yoshinaga Shuji Masumoto Koji Koyama Naoya Kinomura Yuji Matsumoto Taro Kato Satoko Baba Kenji Matsumoto Tomoko Horisawa Hitomi Oki Kazuki Yabuuchi Toru Kodo 《Bioorganic & medicinal chemistry》2017,25(1):293-304
We report the discovery of a novel benzylpiperidine derivative with serotonin transporter (SERT) inhibitory activity and 5-HT1A receptor weak partial agonistic activity showing the antidepressant-like effect. The 3-methoxyphenyl group and the phenethyl group of compound 1, which has weak SERT binding activity, but potent 5-HT1A binding activity, were optimized, leading to compound 35 with potent and balanced dual SERT and 5-HT1A binding activity, but also potent CYP2D6 inhibitory activity. Replacement of the methoxy group in the left part of compound 35 with a larger alkoxy group, such as ethoxy, isopropoxy or methoxy-ethoxy group ameliorated CYP2D6 inhibition, giving SMP-304 as a candidate. SMP-304 with serotonin uptake inhibitory activity and 5-HT1A weak partial agonistic activity, which could work as a 5-HT1A antagonist, displayed faster onset of antidepressant-like effect than a representative SSRI paroxetine in an animal model. 相似文献