全文获取类型
收费全文 | 11772篇 |
免费 | 949篇 |
国内免费 | 385篇 |
专业分类
13106篇 |
出版年
2023年 | 100篇 |
2022年 | 193篇 |
2021年 | 292篇 |
2020年 | 238篇 |
2019年 | 272篇 |
2018年 | 320篇 |
2017年 | 272篇 |
2016年 | 361篇 |
2015年 | 558篇 |
2014年 | 612篇 |
2013年 | 754篇 |
2012年 | 849篇 |
2011年 | 784篇 |
2010年 | 497篇 |
2009年 | 383篇 |
2008年 | 571篇 |
2007年 | 558篇 |
2006年 | 510篇 |
2005年 | 469篇 |
2004年 | 424篇 |
2003年 | 432篇 |
2002年 | 362篇 |
2001年 | 322篇 |
2000年 | 322篇 |
1999年 | 274篇 |
1998年 | 116篇 |
1997年 | 89篇 |
1996年 | 72篇 |
1995年 | 57篇 |
1994年 | 86篇 |
1993年 | 59篇 |
1992年 | 161篇 |
1991年 | 146篇 |
1990年 | 131篇 |
1989年 | 152篇 |
1988年 | 121篇 |
1987年 | 110篇 |
1986年 | 105篇 |
1985年 | 98篇 |
1984年 | 66篇 |
1983年 | 73篇 |
1982年 | 45篇 |
1979年 | 52篇 |
1977年 | 75篇 |
1976年 | 47篇 |
1975年 | 43篇 |
1974年 | 56篇 |
1973年 | 41篇 |
1971年 | 40篇 |
1969年 | 40篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
111.
112.
Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis 总被引:2,自引:0,他引:2
Mazroui R Di Marco S Clair E von Roretz C Tenenbaum SA Keene JD Saleh M Gallouzi IE 《The Journal of cell biology》2008,180(1):113-127
The RNA-binding protein HuR affects cell fate by regulating the stability and/or the translation of messenger RNAs that encode cell stress response proteins. In this study, we delineate a novel regulatory mechanism by which HuR contributes to stress-induced cell death. Upon lethal stress, HuR translocates into the cytoplasm by a mechanism involving its association with the apoptosome activator pp32/PHAP-I. Depleting the expression of pp32/PHAP-I by RNA interference reduces both HuR cytoplasmic accumulation and the efficiency of caspase activation. In the cytoplasm, HuR undergoes caspase-mediated cleavage at aspartate 226. This cleavage activity is significantly reduced in the absence of pp32/PHAP-I. Substituting aspartate 226 with an alanine creates a noncleavable isoform of HuR that, when overexpressed, maintains its association with pp32/PHAP-I and delays the apoptotic response. Thus, we propose a model in which HuR association with pp32/PHAP-I and its caspase-mediated cleavage constitutes a regulatory step that contributes to an amplified apoptotic response. 相似文献
113.
In this paper we study a method for the identification of the unknown parameter of the periodic function and also the first component of the state vector, in a mathematical model which describes the evolution of some diseases with an oro-fecal transmission.To solve the identification problem we use a numerical method to integrate the differential equations system, which reproduces the stability properties of the above mentioned continuous system.The numerical methods which we propose can be applied also to a spatial semi discretization of the reaction-diffusion model which is a diffusive generalization of the system that we consider in this paper.Finally, through an analysis on both the continuous and the discrete system we also obtain a necessary condition on the experimental data in order that a periodic trajectory of the system exists.Work supported by: Progetto Finalizzato Controllo Malattie da Infezione-CNR and by Ministero Pubblica Istruzione 相似文献
114.
Question: How do meteorological variations at seasonal, interannual scales differentially affect the canopy dynamics of four contrasting landscape units within a region? Location: Flooding Pampa, Buenos Aires, Argentina. 5000 km2. Central point: 35°15′S, 57°45′W. Methods: We used a 19‐year series of the normalized difference vegetation index (NDVI) derived from NOAA‐AVHRR PAL (Pathfinder AVHRR Land) images and meteorological data provided by a nearby weather station. The NDVI was used as surrogate of canopy photosynthetic status. The relationship between annually integrated NDVI and meteorological conditions was explored by stepwise multiple regressions for each defined unit. PC A was performed to compare units and growing seasons on a multivariate basis. Results: Mean seasonal NDVI curve was similarly shaped among landscapes. However, the absolute values differed widely. There was high interannual variation so that the mean seasonal pattern was seldom observed in any particular year. Annually integrated NDVI of all landscapes was negatively associated with summer temperature and positively with previous year precipitation. It was also directly related with current year winter precipitation in two landscapes and with summer precipitation in the others. NDVI response to September and March precipitation accounted for some of the differences in interannual variation among landscapes. Conclusions: Our results revealed a strong intra‐regional variation of canopy dynamics, closely linked to landscape (vegetation‐soil) and water availability (mainly in summer and during the previous year). These links may be used to predict forage production rates for livestock. 相似文献
115.
Mycoplasma pneumoniae (Mp) is a frequent cause of Community Acquired Pneumoniae (CAP). The etiological role of Mp is usually suspected using serological assays, but the detection of specific anti-Mp antibodies becomes possible only 1-2 weeks after the primary infection. On the contrary, direct diagnosis using real-time PCR allows an efficient detection of Mp DNA in all the phases of the infection and particularly during early serum negative periods. In this study, we developed a novel Scorpion-probe real-time PCR-based assay. The probe's uni-molecular structure offers thermodynamic advantages owing to its kinetic reaction, providing faster performances compared to a TaqMan-based assay, but maintaining the same sensitivity and specificity. The Scorpion-based assay was employed on 388 clinical samples and compared with conventional qualitative PCR and serological tests. It was found more sensitive because it also allowed the detection of Mp in specimens found negative using classic qualitative PCR, but displaying seropositivity or a later seroconversion. 相似文献
116.
Timmers LF Ducati RG Sánchez-Quitian ZA Basso LA Santos DS de Azevedo WF 《Journal of molecular modeling》2012,18(2):467-479
Cytidine Deaminase (CD) is an evolutionarily conserved enzyme that participates in the pyrimidine salvage pathway recycling cytidine and deoxycytidine into uridine and deoxyuridine, respectively. Here, our goal is to apply computational techniques in the pursuit of potential inhibitors of Mycobacterium tuberculosis CD (MtCDA) enzyme activity. Molecular docking simulation was applied to find the possible hit compounds. Molecular dynamics simulations were also carried out to investigate the physically relevant motions involved in the protein-ligand recognition process, aiming at providing estimates for free energy of binding. The proposed approach was capable of identifying a potential inhibitor, which was experimentally confirmed by IC50 evaluation. Our findings open up the possibility to extend this protocol to different databases in order to find new potential inhibitors for promising targets based on a rational drug design process. 相似文献
117.
Malchiodi-Albedi F Paradisi S Di Nottia M Simone D Travaglione S Falzano L Guidotti M Frank C Cutarelli A Fabbri A Fiorentini C 《PloS one》2012,7(4):e34115
Modulation of cerebral Rho GTPases activity in mice brain by intracerebral administration of Cytotoxic Necrotizing Factor 1 (CNF1) leads to enhanced neurotransmission and synaptic plasticity and improves learning and memory. To gain more insight into the interactions between CNF1 and neuronal cells, we used primary neuronal and astrocytic cultures from rat embryonic brain to study CNF1 effects on neuronal differentiation, focusing on dendritic tree growth and synapse formation, which are strictly modulated by Rho GTPases. CNF1 profoundly remodeled the cytoskeleton of hippocampal and cortical neurons, which showed philopodia-like, actin-positive projections, thickened and poorly branched dendrites, and a decrease in synapse number. CNF1 removal, however, restored dendritic tree development and synapse formation, suggesting that the toxin can reversibly block neuronal differentiation. On differentiated neurons, CNF1 had a similar effacing effect on synapses. Therefore, a direct interaction with CNF1 is apparently deleterious for neurons. Since astrocytes play a pivotal role in neuronal differentiation and synaptic regulation, we wondered if the beneficial in vivo effect could be mediated by astrocytes. Primary astrocytes from embryonic cortex were treated with CNF1 for 48 hours and used as a substrate for growing hippocampal neurons. Such neurons showed an increased development of neurites, in respect to age-matched controls, with a wider dendritic tree and a richer content in synapses. In CNF1-exposed astrocytes, the production of interleukin 1β, known to reduce dendrite development and complexity in neuronal cultures, was decreased. These results demonstrate that astrocytes, under the influence of CNF1, increase their supporting activity on neuronal growth and differentiation, possibly related to the diminished levels of interleukin 1β. These observations suggest that the enhanced synaptic plasticity and improved learning and memory described in CNF1-injected mice are probably mediated by astrocytes. 相似文献
118.
Radaelli A Castiglioni P Centola M Cesana F Balestri G Ferrari AU Di Rienzo M 《American journal of physiology. Heart and circulatory physiology》2006,290(1):H357-H364
Spectral analysis of cardiovascular signals has been extensively used to investigate circulatory homeostatic mechanisms. However, the nature of very low-frequency (VLF) fluctuations remains unclear. Because we previously observed enhanced VLF fluctuations in blood pressure (BP) in the sympathectomized rat (a model characterized by markedly increased plasma epinephrine levels), the aims of our study were to assess whether the genesis of VLF fluctuations in BP depends on circulating catecholamines and to determine which adrenergic receptor(s) and which membrane ion channel(s) are involved. We used continuous intra-arterial BP recordings from unanesthetized unrestrained rats to compute the power of VLF fluctuations in BP in the intact condition, during acute ganglionic blockade with hexamethonium, and after restoration of BP levels by infusion (in addition to hexamethonium) of adrenergic agonists (epinephrine, norepinephrine, and clonidine) or nonadrenergic vasoconstrictors (vasopressin). Effects of infusion of specific adrenergic receptor blockers (propranolol, prazosin, and yohimbine) with hexamethonium and catecholamines and infusion of various membrane ion channel blockers on VLF fluctuations in BP were also evaluated. Our results are as follows. 1) Ganglionic blockade drastically reduced BP levels and VLF fluctuations. 2) All vasoconstrictors restored BP levels, but only adrenergic vasoconstrictors generated striking VLF fluctuations in BP. 3) Catecholamine-induced fluctuations were abolished by alpha2-, but not alpha1- or beta-, adrenergic receptor blockade and by Ba2+-sensitive K+ channel or L-type Ca2+ channel, but not by other ion channel, blockers. We conclude that, in the conscious, unrestrained ganglion-blocked rat, catecholamine infusion generates VLF fluctuations in BP through stimulation of alpha2-receptors and activation of Ba2+-sensitive K+ channels. These fluctuations may have (patho)physiological relevance under conditions of disrupted circulatory homeostasis. 相似文献
119.
M Valente P de Martino Rosaroll C De Santo S Di Meo T De Leo 《Archives internationales de physiologie et de biochimie》1989,97(6):427-430
Confirming the literature data the authors describe that the heart rate is smaller in the newborn rats than in adult ones and increases until the adult values during the first two weeks of life. On the other hand, the blood thyroid hormone exhibits the same pattern, showing an early postnatal increment. As, according the Adolph's data (1967), the heart rate enhancement is not due to the catecholamines, the authors suppose that such enhancement might conceivably depend on thyroid hormone increment. 相似文献
120.