全文获取类型
收费全文 | 69992篇 |
免费 | 2881篇 |
国内免费 | 1911篇 |
出版年
2023年 | 654篇 |
2022年 | 842篇 |
2021年 | 2123篇 |
2020年 | 1252篇 |
2019年 | 1657篇 |
2018年 | 1351篇 |
2017年 | 979篇 |
2016年 | 1568篇 |
2015年 | 3479篇 |
2014年 | 6806篇 |
2013年 | 6274篇 |
2012年 | 4921篇 |
2011年 | 5569篇 |
2010年 | 3923篇 |
2009年 | 3394篇 |
2008年 | 3500篇 |
2007年 | 3812篇 |
2006年 | 2435篇 |
2005年 | 2069篇 |
2004年 | 1294篇 |
2003年 | 1081篇 |
2002年 | 920篇 |
2001年 | 657篇 |
2000年 | 579篇 |
1999年 | 597篇 |
1998年 | 557篇 |
1997年 | 440篇 |
1996年 | 497篇 |
1995年 | 621篇 |
1994年 | 529篇 |
1993年 | 583篇 |
1992年 | 523篇 |
1991年 | 552篇 |
1990年 | 458篇 |
1989年 | 469篇 |
1988年 | 468篇 |
1987年 | 378篇 |
1986年 | 351篇 |
1985年 | 589篇 |
1984年 | 883篇 |
1983年 | 571篇 |
1982年 | 753篇 |
1981年 | 733篇 |
1980年 | 539篇 |
1979年 | 526篇 |
1978年 | 330篇 |
1977年 | 340篇 |
1976年 | 312篇 |
1974年 | 226篇 |
1973年 | 230篇 |
排序方式: 共有10000条查询结果,搜索用时 146 毫秒
71.
Kiyohiko Sugano 《化学与生物多样性》2009,6(11):2014-2029
Bile micelles play an important role in oral absorption of low‐solubility compounds. Bile micelles can affect solubility, dissolution rate, and permeability. For the pH–solubility profile in bile micelles, the Henderson–Hasselbalch equation should be modified to take bile‐micelle partition into account. For the dissolution rate, in the Nernst–Brunner equation, the effective diffusion coefficient in bile‐micelle media should be used instead of the monomer diffusion coefficient. The diffusion coefficient of bile micelles is 8‐ to 18‐fold smaller than that of monomer molecules. For permeability, the effective diffusion coefficient in the unstirred water layer adjacent to the epithelial membrane, and the free fraction at the epithelial membrane surface should be taken into account. The importance of these aspects is demonstrated here using several in vivo and clinical oral‐absorption data of low‐solubility model compounds. Using the theoretical equations, the food effect on oral absorption is further discussed. 相似文献
72.
Alexander G. Volkov Astian J. Waite Joseph D. Wooten Vladislav S. Markin 《Plant signaling & behavior》2012,7(2):282-284
The circadian clock regulates a wide range of electrophysiological and developmental processes in plants. Here, we discuss the direct influence of a circadian clock on biologically closed electrochemical circuits in vivo. The biologically closed electrochemical circuits in the leaves of C. miniata (Kaffir lily), Aloe vera and Mimosa pudica, which regulate their physiology, were analyzed using the charge stimulation method. Plants are able to memorize daytime and nighttime. Even at continuous light or darkness, plants recognize nighttime or daytime and change the input resistance. The circadian clock can be maintained endogenously and has electrochemical oscillators, which can activate ion channels in biologically closed electrochemical circuits. The activation of voltage gated channels depends on the applied voltage, electrical charge, and the speed of transmission of electrical energy from the electrostimulator to plants. 相似文献
73.
Björn Lemmer 《Biological Rhythm Research》2016,47(6):919-925
The aim of the study was to compare an often-used method to measure blood pressure (BP) using a tail-cuff (TC) device, with radiotelemetry (RT) which allows to sample data on heart rate (HR) and BP in freely moving rodents without any restraint in behaviour. Data were collected in male normotensive Wistar-Kyoto rats and in spontaneously hypertensive rats. Experiments were performed under 12:12 h light–dark conditions (lights on at 07:00 h) with simulated dawn and dusk for 45 min. Experiments were performed at 08:00–10:00 h (rest phase) and at 20:00–22:00 h (activity phase) under control conditions and after treatment with the beta-adrenoceptor blocker metoprolol (8 mg/kg). For TC, the Harvard BP Monitoring System (Edenbrigde, England) and for RT radio transmitters (Dataquest IV system, TA11PA-C40, DSI, St. Paul, Minnesota, USA) were used. Rats bearing the TC device were also monitored under RT. The experiments show that TC significantly increased HR and both systolic and diastolic BP in both strains and both at L and D. Metoprolol reduced TC-induced HR but left BP increase uneffected. The study shows that RT is the method of choice to monitor BP and HR in rodents, TC is not suitable. 相似文献
74.
75.
Xiu-Zhen Zhang Xue-Juan Li Hong-Fang Ji 《Biochemical and biophysical research communications》2009,383(3):275-279
Despite the rapid technical progress in pharmaceutical industry in the past decade, it is still a great challenge to find new drugs and the situation seems more and more serious. However, the history of pharmaceutical industry clearly indicated that the significance of drug discovery went far beyond providing new drugs. For instance, drugs or candidates could be used as selective probes to reveal novel cellular mechanisms, which is a fundamental tenet of chemical biology. More interestingly, accumulating evidence indicates that drugs and candidates can find important use in stem cell biology. Not only approved drugs but also undeveloped pharmacological agents could serve as efficient agents to regulate stem cell fate. Moreover, the target and activity knowledge accumulated during the drug discovery process will help select the stem cell fate modulators in a rational manner. As the progress in stem cell biology will bring positive influence to drug discovery, it can be expected that the current drug discovery efforts will finally bear great fruits in the future. 相似文献
76.
77.
《Bioorganic & medicinal chemistry》2016,24(18):4363-4371
Legionella pneumophila is an aerobic, Gram-negative bacterium of the genus Legionella, which constitutes the major causative agent of Legionnaires’ disease. Recently a nucleoside triphosphate diphosphohydrolase (NTPDase) from L. pneumophila was identified and termed Lp1NTPDase; it was found to be a structural and functional homolog of mammalian NTPDases catalyzing the hydrolysis of ATP to ADP and ADP to AMP. Its activity is believed to contribute to the virulence of Legionella pneumophila. Therefore Lp1NTPDase inhibitors are considered as novel antibacterial drugs. However, only weakly potent compounds are available so far. In the present study, a capillary electrophoresis (CE)-based enzyme assay for monitoring the Lp1NTPDase activity was established. The enzymatic reaction was performed in a test tube followed by separation of substrate and products by CE and subsequent quantification by UV analysis. After kinetic characterization of the enzyme, a series of 1-amino-4-ar(alk)ylamino-2-sulfoanthraquinone derivatives structurally related to the anthraquinone dye Reactive Blue 2, a non-selective ecto-NTPDase inhibitor, was investigated for inhibitory activity on Lp1NTPDase using the CE-based enzyme assay. Derivatives bearing a large lipophilic substituent (e.g., fused aromatic rings) in the 4-position of the 1-amino-2-sulfoanthraquinone showed the highest inhibitory activity. Compounds with IC50 values in the low micromolar range were identified. The most potent inhibitor was 1-amino-4-[phenanthrene-9-yl-amino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (28, PSB-16131), with an IC50-value of 4.24 μM. It represents the most potent Lp1NTPDase inhibitor described to date. These findings may serve as a starting point for further optimization. Lp1NTPDase inhibition provides a novel approach for the (immuno)therapy of Legionella infections. 相似文献
78.
At room temperature, the chlorophyll (Chl) a fluorescence induction (FI) kinetics of plants, algae and cyanobacteria go through two maxima, P at ∼ 0.2-1 and M at ∼ 100-500 s, with a minimum S at ∼ 2-10 s in between. Thus, the whole FI kinetic pattern comprises a fast OPS transient (with O denoting origin) and a slower SMT transient (with T denoting terminal state). Here, we examined the phenomenology and the etiology of the SMT transient of the phycobilisome (PBS)-containing cyanobacterium Synechococcus sp PCC 7942 by modifying PBS → Photosystem (PS) II excitation transfer indirectly, either by blocking or by maximizing the PBS → PS I excitation transfer. Blocking the PBS → PS I excitation transfer route with N-ethyl-maleimide [NEM; A. N. Glazer, Y. Gindt, C. F. Chan, and K.Sauer, Photosynth. Research 40 (1994) 167-173] increases both the PBS excitation share of PS II and Chl a fluorescence. Maximizing it, on the other hand, by suspending cyanobactrial cells in hyper-osmotic media [G. C. Papageorgiou, A. Alygizaki-Zorba, Biochim. Biophys. Acta 1335 (1997) 1-4] diminishes both the PBS excitation share of PS II and Chl a fluorescence. Here, we show for the first time that, in either case, the slow SMT transient of FI disappears and is replaced by continuous P → T fluorescence decay, reminiscent of the typical P → T fluorescence decay of higher plants and algae. A similar P → T decay was also displayed by DCMU-treated Synechococcus cells at 2 °C. To interpret this phenomenology, we assume that after dark adaptation cyanobacteria exist in a low fluorescence state (state 2) and transit to a high fluorescence state (state 1) when, upon light acclimation, PS I is forced to run faster than PS II. In these organisms, a state 2 → 1 fluorescence increase plus electron transport-dependent dequenching processes dominate the SM rise and maximal fluorescence output is at M which lies above the P maximum of the fast FI transient. In contrast, dark-adapted plants and algae exist in state 1 and upon illumination they display an extended P → T decay that sometimes is interrupted by a shallow SMT transient, with M below P. This decay is dominated by a state 1 → 2 fluorescence lowering, as well as by electron transport-dependent quenching processes. When the regulation of the PBS → PS I electronic excitation transfer is eliminated (as for example in hyper-osmotic suspensions, after NEM treatment and at low temperature), the FI pattern of Synechococcus becomes plant-like. 相似文献
79.
Sophie J. Milward Natalie Sebanz 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2016,371(1686)
This opinion piece offers a commentary on the four papers that address the theme of the development of self and other understanding with a view to highlighting the important contribution of developmental research to understanding of mechanisms of social cognition. We discuss potential mechanisms linking self–other distinction and empathy, implications for grouping motor, affective and cognitive domains under a single mechanism, applications of these accounts for joint action and finally consider self–other distinction in group versus dyadic settings. 相似文献
80.
Fátima H. Vaz Patrícia M. Machado Rita D. Brand?o Cátia T. Laranjeira Joana S. Eugénio Aires H. Fernandes Saudade P. André 《The journal of histochemistry and cytochemistry》2007,55(11):1105-1113
Only 20-25% of families screened for BRCA1/2 mutations are found positive. Because only a positive result is informative, we studied the role of BRCA1/2 immunohistochemistry as an additional method for patient selection. From 53 high-risk-affected probands, 18 (34%) had available paraffin blocks of their tumors and were selected for this study. Mutation screening was done by conformation-sensitive gel electrophoresis and multiplex ligation-dependent probe amplification. For immunohistochemistry, 21 neoplastic specimens (15 breast carcinomas, 5 ovary neoplasms, and 1 rectal adenocarcinoma) were analyzed with BRCA1 (monoclonal antibody, Ab-1, oncogene) and BRCA2 (polyclonal antibody, Ab-2, oncogene) antibodies. Absence of the BRCA1 protein was confirmed in negative tumors by Western blotting. Seven patients were positive for BRCA1/2 mutations: 5 for BRCA1 and 2 for BRCA2. Four out of five positive patients had tumors negative for BRCA1 immunostaining, and the remaining 13 BRCA1-negative patients had positive BRCA1 immunostaining in all tumor samples. Sensitivity to predict for BRCA1 mutation carriers was 80%, and specificity was 100%, with a positive predictive value of 100% and a negative predictive value of 93%. This correlation was statistically significant (p=0.001). No correlation was observed for BRCA2. If larger studies confirm these results, high-risk patients with BRCA1-negative tumors should be screened first for this gene. 相似文献