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121.
122.
Ying?Wu Rui?Wu Bangjiao?Zhang Tingting?Jiang Ning?Li Kai?Qian Bao?LiuEmail author Jian?ZhangEmail author 《Plant Growth Regulation》2012,66(2):137-143
Gardenia jasminoides Ellis is an evergreen tropical plant and favorite to gardeners throughout the world. Several studies have documented that
in vitro micropropagation can be used for clonal propagation of G. jasminoides Ellis, the efficiency remained low. In addition, no information is available on the genetic and epigenetic fidelity of the
micropropagated plants. Here, we report on a simplified protocol for high efficient micropropagation of G. jasminoides Ellis cv. “Kinberly” based on enhanced branching of shoot-tips as explants. The protocol consisted of sequential use of three
media, namely, bud-induction, elongation and root-induction. By using two molecular markers, amplified fragment length polymorphism
(AFLP) and methylation sensitive amplified polymorphism (MSAP), we analyzed the genetic and DNA methylation pattern stability
of 23 morphologically normal plants randomly taken from a sub-population (>100) of micropropagated plants originated from
a single shoot-tip. We found that of >1,000 scored AFLP bands across the 23 micropropagated plants, no incident of genetic
variation was detected. In contrast, of 750 scored MSAP bands, moderate but clear alteration in several DNA methylation patterns
occurred in the majority of the 23 micropropagated plants. The changed methylation patterns involved both CG and CHG sites
representing either hyper- or hypo-methylation, which occurred without altering the total methylation levels partly due to
concomitant hyper- and hypo-methylation alterations. Our results indicated that epigenetic instability in the form of DNA
methylation patterns can be susceptible to the in vitro micropropagation process for G. jasminoides Ellis, and needs to be taken into account in the process of large-scale commercial propagation of this plant. 相似文献
123.
Jun Feng Lu Meng Qing Zhu Bao Cai Xie Xiao Chen Shi Huan Liu Rui Xin Zhang Bo Xia Jiang Wei Wu 《PLoS biology》2022,20(2)
Elevated circulating levels of growth differentiation factor 15 (GDF15) have been shown to reduce food intake and lower body weight through activation of hindbrain receptor glial-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) in rodents and nonhuman primates, thus endogenous induction of this peptide holds promise for obesity treatment. Here, through in silico drug-screening methods, we found that small molecule Camptothecin (CPT), a previously identified drug with potential antitumor activity, is a GDF15 inducer. Oral CPT administration increases circulating GDF15 levels in diet-induced obese (DIO) mice and genetic ob/ob mice, with elevated Gdf15 expression predominantly in the liver through activation of integrated stress response. In line with GDF15’s anorectic effect, CPT suppresses food intake, thereby reducing body weight, blood glucose, and hepatic fat content in obese mice. Conversely, CPT loses these beneficial effects when Gdf15 is inhibited by a neutralizing antibody or AAV8-mediated liver-specific knockdown. Similarly, CPT failed to reduce food intake and body weight in GDF15’s specific receptor GFRAL-deficient mice despite high levels of GDF15. Together, these results indicate that CPT is a promising anti-obesity agent through activation of GDF15-GFRAL pathway.Elevated circulating levels of growth differentiation factor 15 (GDF15) have been shown to reduce food intake and lower body weight in rodents and nonhuman primates. This study reveals that the small molecule Camptothecin induces endogenous GDF15, suppressing food intake and reducing body weight in obese mice, suggesting a promising candidate for anti-obesity treatment. 相似文献
124.
Lambros MP Parsa C Mulamalla H Orlando R Lau B Huang Y Pon D Chow M 《Biochemical and biophysical research communications》2011,411(1):102-106
Mature adipocytes are excellent candidates to influence tumor behavior through heterotypic signaling processes since these cells produce hormones, growth factors, cytokines and other molecules, a heterogeneous group of molecules named adipokines. Using a 2D coculture system, we demonstrate that breast tumor cells previously co-cultivated with mature adipocytes exhibit radioresistance and an earlier and higher increase in the effector kinase Chk1, a phenotype that was associated with decreased cell death as compared to tumor cells grown alone. Interestingly, the adipocytes-induced tumor changes taking place during the coculture time preceding the exposure to IR were sufficient to confer the radioresistant effect. Notorious among the changes brought by adipocytes was the significant increase of IL-6 expression in tumor cells, whose activity may well account for the observed tumor cell protection from IR toxicity. Indeed, our data confirmed the protective role of this cytokine as tumor cells incubated after irradiation with recombinant IL-6 exhibit an increased in Chk1 phosphorylation and a radioresistant phenotype, thus far recapitulating the effects observed in the presence of adipocytes. Our current study sheds light on a new role of tumor-surrounding adipocytes in fostering a radioresistant phenotype in breast tumors, a finding that might have important clinical implications in obese patients that frequently exhibit aggressive diseases. 相似文献
125.
Trey K. Sato Mary Tremaine Lucas S. Parreiras Alexander S. Hebert Kevin S. Myers Alan J. Higbee Maria Sardi Sean J. McIlwain Irene M. Ong Rebecca J. Breuer Ragothaman Avanasi Narasimhan Mick A. McGee Quinn Dickinson Alex La Reau Dan Xie Mingyuan Tian Jeff S. Piotrowski Jennifer L. Reed Yaoping Zhang Joshua J. Coon Chris Todd Hittinger Audrey P. Gasch Robert Landick 《PLoS genetics》2016,12(11)
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129.
XF Wang XT Tian E Ohkoshi B Qin YN Liu PC Wu MJ Hour HY Hung K Qian R Huang KF Bastow WP Janzen J Jin SL Morris-Natschke KH Lee L Xie 《Bioorganic & medicinal chemistry letters》2012,22(19):6224-6228
Based on a shared structural core of diarylamine in several known anticancer drugs as well as a new cytotoxic hit 6-chloro-2-(4-cyanophenyl)amino-3-nitropyridine (7), 30 diarylamines and diarylethers were designed, synthesized, and evaluated for cytotoxic activity against A549, KB, KB-vin, and DU145 human tumor cell lines (HTCL). Four new leads 11e, 12, 13a, and 13b were discovered with GI(50) values ranging from 0.33 to 3.45μM. Preliminary SAR results revealed that a diarylamine or diarylether could serve as an active structural core, meta-chloro and ortho-nitro groups on the A-ring (either pyridine or phenyl ring) were necessary and crucial for cytotoxic activity, and the para-substituents on the other phenyl ring (B-ring) were related to inhibitory selectivity for different tumor cells. In an investigation of potential biological targets of the new leads, high thoughput kinase screening discovered that new leads 11e, 12 and 13b especially inhibit Mer tyrosine kinase, a proto-oncogene associated with munerous tumor types, with IC(50) values of 2.2-3.0μM. Therefore, these findings provide a good starting point to optimize a new class of compounds as potential anticancer agents, particularly targeting Mer tyrosine kinase. 相似文献
130.
Sun Y Li T Chen H Zhang K Zheng K Mu Y Yan G Li W Shen J Luo G 《The Journal of biological chemistry》2004,279(36):37235-37240
Glutathione peroxidase (GPX) is one of the most crucial antioxidant enzymes in a variety of organisms. Here we described a new strategy for generating a novel GPX mimic by combination of a phage-displayed random 15-mer peptide library followed by computer-aided rational design and chemical mutation. The novel GPX mimic is a homodimer consisting of a 15-mer selenopeptide with an appropriate catalytic center, a specific binding site for substrates, and high catalytic efficiency. Its steady state kinetics was also studied, and the values of k(cat)/K(m)(GSH) and k(cat)/ K(mH(2)O(2)) were found to be similar to that of native GPX and the highest among the existing GPX mimics. Moreover, the novel GPX mimic was confirmed to have a strong antioxidant ability to inhibit lipid peroxidation by measuring the content of malondialdehyde, cell viability, and lactate dehydrogenase activity. Importantly, the novel GPX mimic can penetrate into the cell membrane because of its small molecular size. These characteristics endue the novel mimic with potential perspective for pharmaceutical applications. 相似文献