全文获取类型
收费全文 | 20393篇 |
免费 | 1501篇 |
国内免费 | 8篇 |
出版年
2023年 | 184篇 |
2022年 | 361篇 |
2021年 | 665篇 |
2020年 | 447篇 |
2019年 | 553篇 |
2018年 | 699篇 |
2017年 | 636篇 |
2016年 | 864篇 |
2015年 | 1142篇 |
2014年 | 1258篇 |
2013年 | 1452篇 |
2012年 | 1697篇 |
2011年 | 1530篇 |
2010年 | 919篇 |
2009年 | 822篇 |
2008年 | 1023篇 |
2007年 | 1026篇 |
2006年 | 845篇 |
2005年 | 780篇 |
2004年 | 700篇 |
2003年 | 616篇 |
2002年 | 579篇 |
2001年 | 299篇 |
2000年 | 256篇 |
1999年 | 231篇 |
1998年 | 158篇 |
1997年 | 118篇 |
1996年 | 118篇 |
1995年 | 107篇 |
1994年 | 91篇 |
1993年 | 64篇 |
1992年 | 119篇 |
1991年 | 130篇 |
1990年 | 122篇 |
1989年 | 88篇 |
1988年 | 86篇 |
1987年 | 89篇 |
1986年 | 100篇 |
1985年 | 76篇 |
1984年 | 82篇 |
1983年 | 70篇 |
1982年 | 56篇 |
1981年 | 58篇 |
1980年 | 38篇 |
1979年 | 46篇 |
1978年 | 51篇 |
1977年 | 41篇 |
1975年 | 50篇 |
1974年 | 36篇 |
1973年 | 36篇 |
排序方式: 共有10000条查询结果,搜索用时 22 毫秒
991.
Gilson Stanski Alícia Giolo Hippólito Rogério C. Costa Antonio L. Castilho 《Invertebrate reproduction & development.》2019,63(1):67-75
We aimed to study the fecundity and reproductive investment of Loxopagurus loxochelis under different environmental conditions. In total, 67 ovigerous females were analyzed, 20 from Macaé, 26 from Ubatuba and 21 from Cananéia. The cephalothoracic shield length, fecundity and reproductive investment (Ubatuba 10.2%, Macaé 8.9% and Cananéia 7.5%) were different among the regions (ANCOVA, p < 0.05), caused by different abiotic resources and environmental characteristics found in each sampling region. Cananéia had the smallest individuals and low availability of adequate shells to hermit crabs, a condition that may have affected the growth and reproduction of the animals. Macaé has a continuous transport of nutrients such as nitrogen and phosphorus to the surface promoted by the Cabo Frio Upwelling zone, which may be a favourable condition for plankton production and, consequently, the extended ‘match/mismatch’ adjustment of spawning females of L. loxochelis. We propose that the highest reproductive investment on the Ubatuba coast is a consequence of regional environmental scenarios of waters colder than the Cananéia region, i.e. females concentrate more energy to reproduce seasonally. Thus, we proved that patterns of L. loxochelis’ reproduction can change on a regional scale according to the local condition of shell supply and water temperature. 相似文献
992.
Daniel Ruivo Marques Paula Castilho Ana Allen Gomes Anabela Pereira 《Chronobiology international》2019,36(4):541-547
It is well established in the literature that morning-type individuals present better health indicators than evening-types. Mindfulness is considered an adaptive self-regulation skill associated with well-being and physical and mental health. However, there is scarce studies that relate chronotype and mindfulness. Thus, in this research, our aim was to study the relationship between chronotype and mindfulness-related variables. For this purpose, a sample composed of 483 participants from the community was recruited through an online survey and invited to fill out the Five Facet Mindfulness Questionnaire, the Self-Compassion Scale, and the Composite Morningness Scale. Regarding mindfulness measure, the results indicated that morning-types presented higher levels of “acting with awareness” than intermediate and evening-types. Additionally, as to self-compassion measure, morning-types presented higher levels of “mindfulness” and “overall self-compassion” than intermediate and evening-types. The remaining associations examined were not statistically significant. In sum, the morning-types showed higher scores in some of the mindfulness and self-compassion scales which seem to suggest that this morningness tendency may function as protective factor concerning eventual disorders´ development. Nonetheless, more systematic studies are needed to better understand this association and subsequently foster changes for psychological intervention. 相似文献
993.
Sofia S Pereira Mariana P Monteiro Madalena M Costa Jorge Ferreira Marco G Alves Pedro F Oliveira Ivana Jarak Duarte Pignatelli 《Journal of cellular biochemistry》2019,120(1):894-906
Unraveling molecular mechanisms that regulate tumor development and proliferation is of the utmost importance in the quest to decrease the high mortality rate of adrenocortical carcinomas (ACC). Our aim was to evaluate the role of two of the mitogen-activated protein kinase (MAPK) signaling pathways (extracellular signal-regulated protein kinases [ERKs 1/2] and p38) in the adrenocortical tumorigenesis, as well as the therapeutic potential of MAPK/ERK inhibition. ERKs 1/2 and p38 activation were evaluated in incidentalomas (INC; n = 10), benign Cushing's syndrome (BCS; n = 12), malignant Cushing's syndrome (MCS; n = 6) and normal adrenal glands (NAG; 8). ACC cell line (H295R) was used to evaluate the ability of PD184352 (0.1, 1, and 10 µM), a specific MEK-MAPK-ERK pathway inhibitor, to modulate cell proliferation, viability, metabolism, and steroidogenesis. ERKs 1/2 activation was significantly higher in MCS (2.83 ± 0.17) compared with NAG (1.00 ± 0.19 “arbitrary units”), INC (1.20 ± 0.13) and BCS (2.09 ± 0.09). Phospho-p38 expression was absent in all the MCS analyzed. MAPK/ERK kinase (MEK) inhibition with PD184352 significantly decreased proliferation as well as steroidogenesis and also increased the redox state of the H295R cells. This data suggests that MEK-MAPK-ERK signaling has a role in adrenocortical tumorigenesis that could be potentially used as a diagnostic marker for malignancy and targeted treatment in ACC. 相似文献
994.
995.
Wagner D. Vital Heron F. V. Torquato Larissa de Oliveira Passos Jesus Wagner Alves de Souza Judice Maria Fátima das G. F. da Silva Tiago Rodrigues Giselle Zenker Justo Thiago A. M. Veiga Edgar J. Paredes-Gamero 《Journal of cellular biochemistry》2019,120(6):9608-9623
Several molecules extracted from natural products exhibit different biological activities, such as ion channel modulation, activation of signaling pathways, and anti-inflammatory or antitumor activity. In this study, we tested the antitumor ability of natural compounds extracted from the Raputia praetermissa plant. Among the compounds tested, an alkaloid, here called compound S4 (4-Deoxyraputindole C), showed antitumor effects against human tumor lineages. Compound S4 was the most active against Raji, a lymphoma lineage, promoting cell death with characteristics that including membrane permeabilization, dissipation of the mitochondrial potential, increased superoxide production, and lysosomal membrane permeabilization. The use of cell death inhibitors such as Z-VAD-FMK (caspase inhibitor), necrostatin-1 (receptor-interacting serine/threonine-protein kinase 1 inhibitor), E-64 (cysteine peptidases inhibitor), and N-acetyl- L -cysteine (antioxidant) did not decrease compound S4-dependent cell death. Additionally, we tested the effect of cellular activity on adherent human tumor cells. The highest reduction of cellular activity was observed in A549 cells, a lung carcinoma lineage. In this lineage, the effect on the reduction of the cellular activity was due to cell cycle arrest, without plasma membrane permeabilization, loss of the mitochondrial potential or lysosomal membrane permeabilization. Compound S4 was able to inhibit cathepsin B and L by a nonlinear competitive (negative co-operativity) and simple-linear competitive inhibitions, respectively. The potency of inhibition was higher against cathepsin L. Compound S4 promoted cell cycle arrest at G 0 and G 2 phase, and increase the expression of p16 and p21 proteins. In conclusion, compound S4 is an interesting molecule against cancer, promoting cell death in the human lymphoma lineage Raji and cell cycle arrest in the human lung carcinoma lineage A549. 相似文献
996.
Mariana Ilha Ketlen da Silveira Moraes Francieli Rohden Leo Anderson Meira Martins Radovan Borojevic Guido Lenz Florencia Barbé-Tuana Fátima Costa Rodrigues Guma 《Journal of cellular biochemistry》2019,120(11):19031-19043
Caveolin-1 (Cav-1) expression is increased in hepatic stellate cells (HSC) upon liver cirrhosis and it functions as an integral membrane protein of lipid rafts and caveolae that regulates and integrates multiple signals as a platform. This study aimed to evaluate the role of Cav-1 in HSC. Thus, the effects of exogenous expression of Cav-1 in GRX cells, a model of activated HSC, were determined. Here, we demonstrated through evaluating well-known HSC activation markers – such as α-smooth muscle actin, collagen I, and glial fibrillary acidic protein – that up regulation of Cav-1 induced GRX to a more activated phenotype. GRXEGFP-Cav1 presented an increased migration, an altered adhesion pattern, a reorganization f-actin cytoskeleton, an arrested cell cycle, a modified cellular ultrastructure, and a raised endocytic flux. Based on this, GRX EGFP-Cav1 represents a new cellular model that can be an important tool for understanding of events related to HSC activation. Furthermore, our results reinforce the role of Cav-1 as a molecular marker of HSC activation. 相似文献
997.
998.
Antonio Marinho da Silva Neto Samuel Reghim Silva Michele Vendruscolo Carlo Camilloni Rinaldo Wander Montalvão 《Proteins》2019,87(4):302-312
Here a differential geometry (DG) representation of protein backbone is explored on the analyses of protein conformational ensembles. The protein backbone is described by curvature, κ, and torsion, τ, values per residue and we propose 1) a new dissimilarity and protein flexibility measurement and 2) a local conformational clustering method. The methods were applied to Ubiquitin and c-Myb-KIX protein conformational ensembles and results show that κ\τ metric space allows to properly judge protein flexibility by avoiding the superposition problem. The dmax measurement presents equally good or superior results when compared to RMSF, especially for the intrinsically unstructured protein. The clustering method is unique as it relates protein global to local dynamics by providing a global clustering solutions per residue. The methods proposed can be especially useful to the analyses of highly flexible proteins. The software written for the analyses presented here is available at https://github.com/AMarinhoSN/FleXgeo for academic usage only. 相似文献
999.
Navid Sahebekhtiari Paula Fernandez-Guerra Zahra Nochi Jasper Carlsen Peter Bross Johan Palmfeldt 《生物化学与生物物理学报:疾病的分子基础》2019,1865(1):126-135
The mitochondrial enzyme ETHE1 is a persulfide dioxygenase essential for cellular sulfide detoxification, and its deficiency causes the severe and complex inherited metabolic disorder ethylmalonic encephalopathy (EE). In spite of well-described clinical symptoms of the disease, detailed cellular and molecular characterization is still ambiguous. Cellular redox regulation has been described to be influenced in ETHE1 deficient cells, and to clarify this further we applied image cytometry and detected decreased levels of reduced glutathione (GSH) in cultivated EE patient fibroblast cells. Cell growth initiation of the EE patient cells was impaired, whereas cell cycle regulation was not. Furthermore, Seahorse metabolic analyzes revealed decreased extracellular acidification, i. e. decreased lactate formation from glycolysis, in the EE patient cells. TMT-based large-scale proteomics was subsequently performed to broadly elucidate cellular consequences of the ETHE1 deficiency. More than 130 proteins were differentially regulated, of which the majority were non-mitochondrial. The proteomics data revealed a link between ETHE1-deficiency and down-regulation of several ribosomal proteins and LIM domain proteins important for cellular maintenance, and up-regulation of cell surface glycoproteins. Furthermore, several proteins of endoplasmic reticulum (ER) were perturbed including proteins influencing disulfide bond formation (e.g. protein disulfide isomerases and peroxiredoxin 4) and calcium-regulated proteins. The results indicate that decreased level of reduced GSH and alterations in proteins of ribosomes, ER and of cell adhesion lie behind the disrupted cell growth of the EE patient cells. 相似文献
1000.
João Paulo Araújo Fernandes de Queiroz João Batista Freire de Souza Jr Vanessa Raquel de Morais Oliveira Thibério de Souza Castelo Maiko Roberto Tavares Dantas Leonardo Lelis de Macedo Costa 《Biological Rhythm Research》2019,50(2):232-244
This study aimed to evaluate the diurnal variation of the sensible heat transfer in red-rumped agoutis (Dasyprocta leporina) bred in captivity in a semi-arid environment. In addition, we seek to identify thermal windows by infrared thermography during the daytime period (07:00, 09:00, 11:00, 14:00, and 16:00). The body surface temperature was higher in the pinna (36.84 ± 0.11 °C), followed by the hind limbs (36.55 ± 0.11 °C). These body regions were primarily responsible for heat loss by radiation (which was 10.13 ± 1.17 W m?2 and 11.19 ± 1.17 W m?2, respectively), and acted like biological thermal windows. Heat transfer by convection was more intense in the body trunk and hind limbs at all times of the day. Thus, sensible heat transfer is important for maintaining homeothermy in red-rumped agouti in hot environments. In conclusion, these rodents use specialized body regions (pinna and hind limbs) for heat transfer. 相似文献