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41.
A novel chemical tool compound that is an antagonist of brassinolide (BL, 1)-induced rice lamina joint inclination was developed. Although 2-O-, 3-O-, 22-O-, or 23-O-methylation of BL causes a critical decrease in biological activity,5 a crystal structure of the extracellular leucine-rich repeat (LRR) domain of BRASSINOSTEROID-INSENSITIVE I (BRI1) bound to BL3, 4 indicates that the loss of activity of the O-methylated BL may result from not only the low affinity to BRI1, but also from blocking the interaction with another BR signaling factor, a partner protein of BRI1 (e.g., BRI1-ASSOCIATED KINASE 1, BAK1). On the basis of this hypothesis we synthesized the BL 2,3-acetonide 2, the 22,23-acetonide 3, and the 2,3:22,23-diacetonide 4 to assess the possibility of 2-O- and 3-O- or/and 22-O- and 23-O-alkylated BL as an antagonist in BR signaling evoked by exogenously applied BL. The 2,3-acetonide 2 more strongly inhibited the lamina inclination caused by BL relative to the 22,23-acetonide 3, whereas the diacetonide 4 had no effect most likely due to its increased hydrophobicity. This suggested that the 2,3-hydroxyl groups of BL play a more significant role in the interaction with a BRI1 partner protein rather than BRI1 itself in rice lamina joint inclination. Taken together it was demonstrated that BL, the most potent agonist of BRI1, is transformed into an antagonist by functionalization of the 2,3-dihydroxyl groups as the acetonide. This finding opens the door to the potential development of a chemical tool that modulates protein–protein interactions in the BR signaling pathway to dissect the BR-dependent processes. 相似文献
42.
Kouta Takeda Takuya Ishida Kiyohiko Igarashi Masahiro Samejima Hiroyuki Ohno 《Bioscience, biotechnology, and biochemistry》2013,77(7):1195-1198
Pyrroloquinoline quinone-dependent quinoprotein alcohol dehydrogenases (PQQ-ADH) require ammonia or primary amines as activators in in vitro assays with artificial electron acceptors. We found that PQQ-ADH from Pseudomonas putida KT2440 (PpADH) was activated by various primary amines, di-methylamine, and tri-methylamine. The alcohol oxidation activity of PpADH was strongly enhanced and the affinity for substrates was also improved by pentylamine as an activator. 相似文献
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Akihito Tanaka Knut Woltjen Katsuya Miyake Akitsu Hotta Makoto Ikeya Takuya Yamamoto Tokiko Nishino Emi Shoji Atsuko Sehara-Fujisawa Yasuko Manabe Nobuharu Fujii Kazunori Hanaoka Takumi Era Satoshi Yamashita Ken-ichi Isobe En Kimura Hidetoshi Sakurai 《PloS one》2013,8(4)
The establishment of human induced pluripotent stem cells (hiPSCs) has enabled the production of in vitro, patient-specific cell models of human disease. In vitro recreation of disease pathology from patient-derived hiPSCs depends on efficient differentiation protocols producing relevant adult cell types. However, myogenic differentiation of hiPSCs has faced obstacles, namely, low efficiency and/or poor reproducibility. Here, we report the rapid, efficient, and reproducible differentiation of hiPSCs into mature myocytes. We demonstrated that inducible expression of myogenic differentiation1 (MYOD1) in immature hiPSCs for at least 5 days drives cells along the myogenic lineage, with efficiencies reaching 70–90%. Myogenic differentiation driven by MYOD1 occurred even in immature, almost completely undifferentiated hiPSCs, without mesodermal transition. Myocytes induced in this manner reach maturity within 2 weeks of differentiation as assessed by marker gene expression and functional properties, including in vitro and in vivo cell fusion and twitching in response to electrical stimulation. Miyoshi Myopathy (MM) is a congenital distal myopathy caused by defective muscle membrane repair due to mutations in DYSFERLIN. Using our induced differentiation technique, we successfully recreated the pathological condition of MM in vitro, demonstrating defective membrane repair in hiPSC-derived myotubes from an MM patient and phenotypic rescue by expression of full-length DYSFERLIN (DYSF). These findings not only facilitate the pathological investigation of MM, but could potentially be applied in modeling of other human muscular diseases by using patient-derived hiPSCs. 相似文献
44.
Huifang Hao Yutaka Maeda Takuya Fukazawa Tomoki Yamatsuji Munenori Takaoka Xiao-Hong Bao Junji Matsuoka Tatsuo Okui Tsuyoshi Shimo Nagio Takigawa Yasuko Tomono Motowo Nakajima Iris M. Fink-Baldauf Sandra Nelson William Seibel Ruben Papoian Jeffrey A. Whitsett Yoshio Naomoto 《PloS one》2013,8(8)
Midkine (MDK) is a heparin-binding growth factor that is highly expressed in many malignant tumors, including lung cancers. MDK activates the PI3K pathway and induces anti-apoptotic activity, in turn enhancing the survival of tumors. Therefore, the inhibition of MDK is considered a potential strategy for cancer therapy. In the present study, we demonstrate a novel small molecule compound (iMDK) that targets MDK. iMDK inhibited the cell growth of MDK-positive H441 lung adenocarcinoma cells that harbor an oncogenic KRAS mutation and H520 squamous cell lung cancer cells, both of which are types of untreatable lung cancer. However, iMDK did not reduce the cell viability of MDK-negative A549 lung adenocarcinoma cells or normal human lung fibroblast (NHLF) cells indicating its specificity. iMDK suppressed the endogenous expression of MDK but not that of other growth factors such as PTN or VEGF. iMDK suppressed the growth of H441 cells by inhibiting the PI3K pathway and inducing apoptosis. Systemic administration of iMDK significantly inhibited tumor growth in a xenograft mouse model in vivo. Inhibition of MDK with iMDK provides a potential therapeutic approach for the treatment of lung cancers that are driven by MDK. 相似文献
45.
Takuya Fukuda Hideki Wagatsuma Yoshifumi Kominami Yasuyuki Nogata Erina Yoshimura Kazuhiro Chiba Yoshikazu Kitano 《化学与生物多样性》2016,13(11):1502-1510
Creation of new potent antifouling active compounds is important for the development of environmentally friendly antifouling agents. Fifteen isocyanide congeners derived from proteinogenic amino acids were synthesized, and the antifouling activity and toxicity of these compounds against cypris larvae of the barnacle Balanus amphitrite were investigated. All synthesized amino acid‐isocyanides exhibited potent anti‐barnacle activity with EC50 values of 0.07 – 10.34 μg/ml after 120 h exposure without significant toxicity. In addition, seven compounds showed more than 95% settlement inhibition of the cypris larvae at 10 μg/ml after 120 h exposure without any mortality observed. Considering their structure, these amino acid‐isocyanides would eventually be biodegraded to their original nontoxic amino acids. These should be useful for further research focused on the development of environmentally friendly antifoulants. 相似文献
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Shingo Hatakeyama Takuya Koie Takuma Narita Shogo Hosogoe Hayato Yamamoto Yuki Tobisawa Tohru Yoneyama Takahiro Yoneyama Yasuhiro Hashimoto Chikara Ohyama 《PloS one》2016,11(2)
ObjectivesTo assess the effects of urinary diversion on renal function, we retrospectively investigated renal function over 5 years after urinary diversion using a propensity score matching strategy.MethodsBetween May 1996 and November 2013, 345 consecutive adult patients underwent radical cystectomy and urinary diversion in our hospital; one hundred and fifteen patients with more than a 5-year follow-up were enrolled. Propensity scores were calculated using logistic analysis, and the data used in the analyses included age, gender, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), clinical tumor stage, presence of cardiovascular disease; hypertension; and type 2 diabetes and preoperative eGFR at the initial visit. Multivariate logistic regression analysis was used to assess the risk factors for stage 3B chronic kidney disease (CKD) after the different types of urinary diversion.ResultsContinent and incontinent diversion were performed in 68 and 47 patients, respectively. The mean preoperative eGFR was significantly lower in the incontinent than in the continent group (P < 0.001). In propensity score-matched patients (n = 34 each), no significant differences were observed in pre- and postoperative eGFR and 5-year eGFR decrease rates between the groups. In the incontinent group, the number of postoperative stage 3B CKD patients was significantly increased than the continent group. Using multivariate analysis, independent risk factors significantly associated with stage 3B CKD at 5 years after surgery were older age, eGFR before surgery, incontinent diversion (cutaneous ureterostomy), and postoperative hydronephrosis.ConclusionsThe types of urinary diversion had no significant impact on renal function decline, whereas older age, preexisting impaired renal function, postoperative hydronephrosis, and cutaneous ureterostomy were independent risk factors for stage 3B CKD at 5 years after radical cystectomy. 相似文献
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