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801.
802.
Isao Sakurada Toshiya Endo Katsuyoshi Hikita Tomokazu Hirabayashi Yoshitaka Hosaka Yutaka Kato Yoshitaka Maeda Shigeki Matsumoto Takashi Mizuno Hiroshi Nagasue Teruyuki Nishimura Shunsuke Shimada Mikihiko Shinozaki Keiko Taguchi Katsutoshi Takeuchi Tooru Yokoyama Alan Hruza Paul Reichert Shoji Furusako 《Bioorganic & medicinal chemistry letters》2017,27(11):2622-2628
Using structure based drug design, novel aminobenzisoxazoles as coagulation factor IXa inhibitors were designed and synthesized. Highly selective inhibition of FIXa over FXa was demonstrated. Anticoagulation profile of selected compounds was evaluated by aPTT and PT tests. In vitro ADMET and pharmacokinetic (PK) profiles were also evaluated. 相似文献
803.
Kentaro Matsuoka Nobutaka Kiyokawa Tomoko Taguchi Jun Matsui Toyo Suzuki Kenichi Mimori Hideki Nakajima Hisami Takenouchi Tang Weiran Yohko U Katagiri Junichiro Fujimoto 《European journal of biochemistry》2002,269(14):3511-3521
The p25(rum1) is an inhibitor of Cdc2 kinase expressed in fission yeast and plays an important role in cell-cycle control. As its amino-acid sequence suggests that p25(rum1) has putative phosphorylation sites for mitogen-activated protein kinase (MAPK), we investigated the ability of MAPK to phosphorylate p25(rum1). Direct in vitro kinase assay using GST-fusion proteins of wild-type as well as various mutants of p25(rum1) demonstrated that MAPK phosphorylates the N-terminal portion of p25(rum1) and residues Thr13 and Ser19 are major phosphorylation sites for MAPK. In addition, phosphorylation of p25(rum1) by MAPK revealed markedly reduced Cdc2 kinase inhibitor ability of the protein. Together with the fact that replacement of both Thr13 and Ser19 with Glu, which mimics the phosphorylated state of these residues, also significantly reduces the activity of p25(rum1) as a Cdc2 inhibitor, it was suggested that the phosphorylation of Thr13 and Ser19 negatively regulates the function of p25(rum1). Further evidence indicates that phosphorylation of Thr13 and Ser19 may retain a negative effect on the function of p25(rum1) even in vivo. Therefore, MAPK may regulate the function of p25(rum1) via phosphorylation of its Thr and Ser residues and thus participate in cell cycle control in fission yeast. 相似文献
804.
805.
Yokoi Haruhiko Shiragami Tsutomu Hirose Jun Kawauchi Takeshi Hinoue Kenichi Fueda Yoshiyuki Nobuhara Kazunori Akazaki Izumi Yasuda Masahide 《World journal of microbiology & biotechnology》2003,19(6):559-563
In order to develop a bactericidal agent operating under visible light irradiation, a silica gel-supported dihydroxo(tetraphenylporphyrinato)antimony(V) complex (SbTPP/SiO2) was prepared. The SbTPP/SiO2 particles irradiated by fluorescent light in a test tube induced remarkable bactericidal activity for Escherichia coli cells. The bactericidal activity of the SbTPP/SiO2 was affected by both the concentration of the SbTPP/SiO2 and the light intensity. Under irradiation by visible light, the SbTPP/SiO2 photocatalyst showed much superior bactericidal activity to the commercially available TiO2. Moreover, under irradiation by sunlight, bactericidal activity of the SbTPP/SiO2 was observed, and the bactericidal effect of the SbTPP/SiO2 particles was effective for continuous treatment on a column photoreactor under fluorescent-light irradiation. 相似文献
806.
Nobuyuki Tanaka Tetsuro Tamai Harunobu Mukaiyama Akihito Hirabayashi Hideyuki Muranaka Takehiro Ishikawa Satoshi Akahane Masuo Akahane 《Bioorganic & medicinal chemistry》2001,9(12)
In a search for novel analogues of β3-adrenoceptor (AR) agonists relaxing the bladder for treatment of urinary dysfunction, 2-[4-(2-{[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)phenoxy]-2-methylpropionic acids (1a–e), into which a fibrate-like structure had been incorporated, were synthesised. Compound 1a was found to be a selective β3-AR agonist in functional assays using the ferret detrusor (β3-AR), rat uterus (β2-AR), and rat atrium (β1-AR); β3: EC50=7.8 nM, β2: IC50=7,300 nM, β1: EC20=23,000 nM. The introduction of a chlorine atom or methyl substituent at the ortho-position on the phenyl ring of 1a further improved β3-AR selectivity. In an in vivo study, 1a lowered intrabladder pressure (ED50=31 μg/kg) in rats, without increasing heart rate, in keeping with the in vitro results. Consequently, it is proposed that 1a and its analogues (1b–e), possess β3-AR agonistic activity in the absence of undesirable β1- or β2-AR mediated actions, and may be useful for clinical treatment and pharmacological studies. 相似文献
807.
Hasegawa Koki Sha Yin Lin Bang Jeong Kyu Kawakami Toru Akaji Kenichi Aimoto Saburo 《International journal of peptide research and therapeutics》2001,8(3-5):277-284
Summary Efficient methods for the preparation of phosphopeptide thioesters were examined, using Fmoc-based solid-phase method. Phosphopeptide
thioesters were obtained in good yields by the use of 1-methylpyrrolidine hexamethyl-eneimine and 1-hydroxybenzotriazole in
a DMSO-DMF (1∶1, v/v) solution for deblocking the Fmoc groups. Epimerization, which is often observed at the C-terminal amino
acid, was effectively suppressed by shortening the time of deblocking process via the use of highly base sensitive Fmoc(2-F)
groups for α-amino protection. 相似文献
808.
H Sprong S Degroote T Claessens J van Drunen V Oorschot B H Westerink Y Hirabayashi J Klumperman P van der Sluijs G van Meer 《The Journal of cell biology》2001,155(3):369-380
Although glycosphingolipids are ubiquitously expressed and essential for multicellular organisms, surprisingly little is known about their intracellular functions. To explore the role of glycosphingolipids in membrane transport, we used the glycosphingolipid-deficient GM95 mouse melanoma cell line. We found that GM95 cells do not make melanin pigment because tyrosinase, the first and rate-limiting enzyme in melanin synthesis, was not targeted to melanosomes but accumulated in the Golgi complex. However, tyrosinase-related protein 1 still reached melanosomal structures via the plasma membrane instead of the direct pathway from the Golgi. Delivery of lysosomal enzymes from the Golgi complex to endosomes was normal, suggesting that this pathway is not affected by the absence of glycosphingolipids. Loss of pigmentation was due to tyrosinase mislocalization, since transfection of tyrosinase with an extended transmembrane domain, which bypassed the transport block, restored pigmentation. Transfection of ceramide glucosyltransferase or addition of glucosylsphingosine restored tyrosinase transport and pigmentation. We conclude that protein transport from Golgi to melanosomes via the direct pathway requires glycosphingolipids. 相似文献
809.
Association studies of CTLA-4, CD28, and ICOS gene polymorphisms with type 1 diabetes in the Japanese population 总被引:4,自引:0,他引:4
Kenji Ihara Saifuddin Ahmed Futoshi Nakao Naoko Kinukawa Ryuichi Kuromaru Nobuo Matsuura Isao Iwata Seiho Nagafuchi Hitoshi Kohno Kenichi Miyako Toshiro Hara 《Immunogenetics》2001,53(6):447-454
Co-stimulatory molecules of CD28, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and the newly identified inducible co-stimulator (ICOS) are expressed on cell surfaces and provide regulatory signals for T-cell activation. Their genes are candidate susceptibility genes for type 1 diabetes because they co-localize to Chromosome 2q33 with the IDDM12 locus. After determining the genomic structure and screening for polymorphisms of the ICOS gene, we performed association studies between newly identified polymorphisms of the ICOS gene, together with known polymorphisms of CD28 and CTLA-4 genes, and type 1 diabetes. The 49A/G dimorphism in exon 1 and the (AT)n in the 3' untranslated region of the CTLA-4 gene were significantly associated with type 1 diabetes. Evaluation of the CTLA-4 49A-3'(AT)n 86-bp haplotype frequency in patients and controls confirmed the results from the analysis of each polymorphic site. Dimorphism in intron 3 of the CD28 gene was associated with type 1 diabetes only in the early-onset group. In contrast, there was no association with the microsatellite polymorphisms in the ICOS gene or dimorphisms in the promotor region of CTLA-4. Of the three genes encoding co-stimulatory molecules, the CTLA-4 gene appears to confer risks for the development of type 1 diabetes. 相似文献
810.