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101.
Teno N Gohda K Wanaka K Sueda T Tsuda Y 《Bioorganic & medicinal chemistry letters》2011,21(21):6305-6309
Lysine-nitrile derivatives having a trisubstituted benzene, which belongs to a new chemical class, were prepared and tested for inhibitory activities against plasmin and the highly homologous plasma kallikrein and urokinase. The use of the novel chemotype in the development of plasmin inhibitors has been demonstrated by derivatives of compound 9. 相似文献
102.
103.
Monotherapy with a novel intervenolin derivative,AS‐1934, is an effective treatment for Helicobacter pylori infection 下载免费PDF全文
104.
Akari Nitta Kazuya Hori Isei Tanida Ayumi Igarashi Yasuyo Deyama Takashi Ueno Eiki Kominami Manabu Sugai Koji Aoki 《Biochemical and biophysical research communications》2019,508(2):521-526
Autophagy, a system for the bulk degradation of intracellular components, is essential for homeostasis and the healthy physiology and development of cells and tissues. Its deregulation is associated with human disease. Thus, methods to modulate autophagic activity are critical for analysis of its role in mammalian cells and tissues. Here we report a method to inhibit autophagy using a mutant variant of the protein ATG7, a ubiquitin E1-like enzyme essential for autophagosome formation. During autophagy, ATG7 activates the conjugation of LC3 (ATG8) with phosphatidylethanolamine (PE) and ATG12 with ATG5. Human ATG7 interactions with LC3 or ATG12 require a thioester bond involving the ATG7 cysteine residue at position 572. We generated TetOff cells expressing mutant ATG7 protein carrying a serine substitution of this critical cysteine residue (ATG7C572S). Because ATG7C572S forms stable intermediate complexes with LC3 or ATG12, its expression resulted in a strong blockage of the ATG-conjugation system and suppression of autophagosome formation. Consequently, ATG7C572S mutant protein can be used as an inhibitor of autophagy. 相似文献
105.
The establishment of IL-2 producing cells by genetic engineering 总被引:4,自引:0,他引:4
Expression plasmids containing human interleukin-2(IL-2) cDNA under the control of viral promoters (SV40 early region, MuLV LTR, HTLV-I LTR, and ASV (Y73) LTR) were introduced into TK- mouse L cells and human FL cells to establish IL-2 producing cells. The highest levels of IL-2 producing clones were obtained in TK+ mouse L cells transformed with a recombinant plasmid having MuLV LTR as a promoter, whereas transformed cells of human FL cells (G418r) were revealed to produce IL-2 at the highest level when the cells were transfected with a plasmid containing HTLV LTR as a promoter. These results suggest that these promoter/enhancer regions possess different cell specificities in gene expression. To obtain higher levels of IL-2 production using gene amplification, the hybrid plasmids containing the hamster DHFR and human IL-2 genes were constructed and transfected into DHFR- CHO cells. DHFR+ colonies produced IL-2 at about the same level as that produced by TK+ L cells transformed with the recombinants containing MuLV LTR. Selection of methotrexate-resistant cells resulted in a 5- to 30-fold increase of IL-2 production. These cells produced IL-2 stably for at least 3 months, even in the absence of methotrexate. 相似文献
106.
107.
Inhibition studies of crystallized rat liver argininosuccinate synthetase [EC 6.3.4.5] are described. 1. L-Argininosuccinate, L-histidine, and L-tryptophan inhibited the enzyme activity at saturating amounts of the substrates. 2. L-Norvaline, L-argininosuccinate, L-arginine, L-isoleucine, and L-valine competitively inhibited the enzyme activity at a low concentration of L-citrulline, with Ki values of 1.3 x 10(4) M, 2.5 X 10(-4) M, 6.7 X 10(-4) M, 6.3 X 10(-4) M, and 6.0 x 10(-4) M, respectively. 3. L-Argininosuccinate and L-arginine competitively inhibited the enzyme activity at a low concentration of L-aspartate, with Ki values of 9.5 x 10(-4) M and 1.2 x 10(-3) M, respectively. 4. The modes of inhibition by L-histidine were mixed-noncompetitive, uncompetitive, and noncompetitive types with respect to L-citrulline, L-aspartate, and ATP, respectively. 5. When the enzyme was preincubated with L-citrulline, the enzyme activity was slightly increased in the presence of a low concentration of L-histidine in the assay mixture. 6. The conformation of the enzyme was markedly changed by the addition of L-histidine as judged from the CD spectrum. This change was partially reversed by incubation with L-citrulline. 相似文献
108.
Purpose
To compare the efficacy, predictability, safety, and induced higher-order aberrations (HOAs) between wavefront-guided and non-wavefront-guided photorefractive keratectomy (PRK).Methods
The Cochrane Central Register of Controlled Trials, PubMED, and EMBASE were searched for randomized controlled trials. Trials meeting the selection criteria were quality appraised, and data was extracted by 2 independent authors. Measures of association were pooled quantitatively using meta-analytical methods. Comparisons between wavefront-guided and non-wavefront-guided ablations were made as pooled odds ratios (ORs) or weighted mean differences. The pooled ORs and 95% confidence intervals (CIs) were computed for efficacy, safety, and predictability. The weighted mean differences and 95% CIs were used to compare induced HOAs.Results
The study covered five trials involving 298 eyes. After wavefront-guided PRK, the pooled OR of achieving an uncorrected distance visual acuity of 20/20 (efficacy) was 1.18 (95% CI, 0.53–2.60; p = 0.69), the pooled OR of achieving a result within ±0.50 diopter of the intended target (predictability) was 0.86 (95% CI, 0.40–1.84; p = 0.70). No study reported a loss of 2 or more lines of Snellen acuity (safety) with either modality. In eyes with wavefront-guided PRK, the postoperative trefoil aberrations (mean difference −0.02; 95% CI, −0.03 to −0.00; p = 0.03) were significantly lower. There were no significant differences between the two groups in the postoperative total HOAs (mean difference −0.04; 95% CI, −0.23 to 0.14; p = 0.63), spherical (mean difference 0.00; 95% CI, −0.08 to 0.09; p = 0.93), and coma (mean difference −0.06; 95% CI, −0.14 to 0.03; p = 0.20) aberrations.Conclusions
According to the meta-analysis, wavefront-guided PRK offered no advantage in efficacy, predictability, or safety measures over non-wavefront-guided PRK, although it may have induced fewer trefoil aberrations. 相似文献109.
Masaya Yamaoka Norikazu Maeda Yasunori Takayama Ryohei Sekimoto Yu Tsushima Keisuke Matsuda Takuya Mori Kana Inoue Hitoshi Nishizawa Makoto Tominaga Tohru Funahashi Iichiro Shimomura 《PloS one》2014,9(11)
Visceral fat adiposity plays an important role in the development of metabolic syndrome. We reported previously the impact of human visceral fat adiposity on gene expression profile of peripheral blood cells. Genes related to circadian rhythm were highly associated with visceral fat area and period homolog 1 (PER1) showed the most significant negative correlation with visceral fat area. However, regulation of adipose Per1 remains poorly understood. The present study was designed to understand the regulation of Per1 in adipose tissues. Adipose Per1 mRNA levels of ob/ob mice were markedly low at 25 and 35 weeks of age. The levels of other core clock genes of white adipose tissues were also low in ob/ob mice at 25 and 35 weeks of age. Per1 mRNA was mainly expressed in the mature adipocyte fraction (MAF) and it was significantly low in MAF of ob/ob mice. To examine the possible mechanisms, 3T3-L1 adipocytes were treated with H2O2, tumor necrosis factor-α (TNF-α), S100A8, and lipopolysaccharide (LPS). However, no significant changes in Per1 mRNA level were observed by these agents. Exposure of cultured 3T3-L1 adipocytes to low temperature (33°C) decreased Per1 and catalase, and increased monocyte chemoattractant protein-1 (Mcp-1) mRNA levels. Hypothermia also worsened insulin-mediated Akt phosphorylation in 3T3-L1 adipocytes. Finally, telemetric analysis showed low temperature of adipose tissues in ob/ob mice. In obesity, adipose hypothermia seems to accelerate adipocyte dysfunction. 相似文献
110.
Spatial variation in phenology can occur at small spatial scales over which individuals can disperse or forage within one generation. Previous studies have assumed that variations in phenological peaks are caused by differences in abiotic environmental characteristics. However, environments should generally be similar among local habitats over small spatial scales. When the local population size is small, the phenological peak of the local population should be strongly affected by the variation in timing expressed by individuals. If a regional population consists of small local subpopulations (e.g., a metapopulation), the stochastic processes regulated by population sizes may explain the spatial variation in phenology. In this study, we quantitatively evaluated the extent of the spatial and annual variations in the breeding phenology of the forest green tree frog, Rhacophorus arboreus habiting a small area (<10 km2). The spatial variation in phenological peaks among 25 breeding sites was large over 6 years. This spatial variation was not explained by differences in air temperature or water depth. Randomization tests revealed that a large portion of the spatial variation could be explained by differences in population size, without considering site-specific factors. Annual variations in phenological peaks tended to be greater for smaller populations. These results imply that the stochastic process might have caused the spatial and annual variations in the phenological peaks of R. arboreus observed in the study region. Understanding spatiotemporal variation in phenology determined by stochastic process would be important to better predict interspecific interactions and (meta)population dynamics at small spatial scales. 相似文献