全文获取类型
收费全文 | 5623篇 |
免费 | 414篇 |
国内免费 | 1篇 |
专业分类
6038篇 |
出版年
2023年 | 50篇 |
2022年 | 85篇 |
2021年 | 167篇 |
2020年 | 114篇 |
2019年 | 137篇 |
2018年 | 170篇 |
2017年 | 159篇 |
2016年 | 253篇 |
2015年 | 319篇 |
2014年 | 351篇 |
2013年 | 387篇 |
2012年 | 527篇 |
2011年 | 446篇 |
2010年 | 250篇 |
2009年 | 248篇 |
2008年 | 311篇 |
2007年 | 260篇 |
2006年 | 265篇 |
2005年 | 248篇 |
2004年 | 242篇 |
2003年 | 209篇 |
2002年 | 190篇 |
2001年 | 53篇 |
2000年 | 41篇 |
1999年 | 55篇 |
1998年 | 57篇 |
1997年 | 43篇 |
1996年 | 31篇 |
1995年 | 30篇 |
1994年 | 34篇 |
1993年 | 26篇 |
1992年 | 27篇 |
1991年 | 23篇 |
1990年 | 21篇 |
1989年 | 17篇 |
1988年 | 10篇 |
1987年 | 12篇 |
1986年 | 15篇 |
1985年 | 20篇 |
1984年 | 8篇 |
1983年 | 16篇 |
1982年 | 19篇 |
1981年 | 12篇 |
1980年 | 6篇 |
1978年 | 9篇 |
1974年 | 6篇 |
1972年 | 6篇 |
1971年 | 5篇 |
1969年 | 5篇 |
1968年 | 7篇 |
排序方式: 共有6038条查询结果,搜索用时 15 毫秒
121.
González S Moreno-Delgado D Moreno E Pérez-Capote K Franco R Mallol J Cortés A Casadó V Lluís C Ortiz J Ferré S Canela E McCormick PJ 《PLoS biology》2012,10(6):e1001347
The role of the pineal gland is to translate the rhythmic cycles of night and day encoded by the retina into hormonal signals that are transmitted to the rest of the neuronal system in the form of serotonin and melatonin synthesis and release. Here we describe that the production of both melatonin and serotonin by the pineal gland is regulated by a circadian-related heteromerization of adrenergic and dopamine D4 receptors. Through α1
B-D4 and β1-D4 receptor heteromers dopamine inhibits adrenergic receptor signaling and blocks the synthesis of melatonin induced by adrenergic receptor ligands. This inhibition was not observed at hours of the day when D4 was not expressed. These data provide a new perspective on dopamine function and constitute the first example of a circadian-controlled receptor heteromer. The unanticipated heteromerization between adrenergic and dopamine D4 receptors provides a feedback mechanism for the neuronal hormone system in the form of dopamine to control circadian inputs. 相似文献
122.
The formation of a through-gut was a key innovation in the evolution of metazoans. There is still controversy regarding the origin of the anus and how it may have been either gained or lost during evolution in different bilaterian taxa. Thus, the study of groups with a blind gut is of great importance for understanding the evolution of this organ system. Here, we describe the morphogenesis and molecular patterning of the blind gut in the sexual triclad Schmidtea polychroa. We identify and analyze the expression of goosecoid, commonly associated with the foregut, and the GATA, ParaHox and T-box genes, members of which commonly are associated with gut regionalization. We show that GATA456a is expressed in the blind gut of triclads, while GATA456b is localized in dorsal parenchymal cells. Goosecoid is expressed in the central nervous system, and the unique ParaHox gene identified, Xlox, is detected in association with the nervous system. We have not isolated any brachyury gene in the T-box complement of S. polychroa, which consists of one tbx1/10, three tbx2/3 and one tbx20. Furthermore, the absence of genes like brachyury and caudal is also present in other groups of Platyhelminthes. This study suggests that GATA456, in combination with foxA, is a gut-specific patterning mechanism conserved in the triclad S. polychroa, while the conserved gut-associated expression of foregut, midgut and hindgut markers is absent. Based on these data and the deviations in spiral cleavage found in more basal flatworms, we propose that the lack of an anus is an innovation of Platyhelminthes. This may be associated with loss of gut gene expression or even gene loss. 相似文献
123.
Fernando J. Yuste-Lisbona Carmen Capel Emilio Sarria Rocío Torreblanca María L. Gómez-Guillamón Juan Capel Rafael Lozano Ana I. López-Sesé 《Molecular breeding : new strategies in plant improvement》2011,27(2):181-192
Powdery mildew caused by Podosphaera xanthii has become a major problem in melon since it occurs all year round irrespective of the growing system. The TGR-1551 melon
genotype was found to be resistant to several melon diseases, among them powdery mildew. However, the corresponding resistance
genes have been never mapped. We constructed an integrated genetic linkage map using an F2 population derived from a cross
between the multi-resistant genotype TGR-1551 and the susceptible Spanish cultivar ‘Bola de Oro’. The map spans 1,284.9 cM,
with an average distance of 3.6 cM among markers, and consists of 354 loci (188 AFLP, 39 RAPD, 111 SSR, 14 SCAR/CAPS/dCAPS,
and two phenotypic traits) distributed in 14 linkage groups. QTL analysis identified one major QTL (Pm-R) on LG V for resistance to races 1, 2, and 5 of powdery mildew. The PM4-CAPS marker is closely linked to the Pm-R QTL at a genetic distance of 1.9 cM, and the PM3-CAPS marker is located within the support interval of this QTL. These codominant
markers, together with the map information reported here, could be used for melon breeding, and particularly for genotyping
selection of resistance to powdery mildew in this vegetable crop species. 相似文献
124.
Orru M Bakešová J Brugarolas M Quiroz C Beaumont V Goldberg SR Lluís C Cortés A Franco R Casadó V Canela EI Ferré S 《PloS one》2011,6(1):e16088
Striatal adenosine A(2A) receptors (A(2A)Rs) are highly expressed in medium spiny neurons (MSNs) of the indirect efferent pathway, where they heteromerize with dopamine D(2) receptors (D(2)Rs). A(2A)Rs are also localized presynaptically in cortico-striatal glutamatergic terminals contacting MSNs of the direct efferent pathway, where they heteromerize with adenosine A(1) receptors (A(1)Rs). It has been hypothesized that postsynaptic A(2A)R antagonists should be useful in Parkinson's disease, while presynaptic A(2A)R antagonists could be beneficial in dyskinetic disorders, such as Huntington's disease, obsessive-compulsive disorders and drug addiction. The aim or this work was to determine whether selective A(2A)R antagonists may be subdivided according to a preferential pre- versus postsynaptic mechanism of action. The potency at blocking the motor output and striatal glutamate release induced by cortical electrical stimulation and the potency at inducing locomotor activation were used as in vivo measures of pre- and postsynaptic activities, respectively. SCH-442416 and KW-6002 showed a significant preferential pre- and postsynaptic profile, respectively, while the other tested compounds (MSX-2, SCH-420814, ZM-241385 and SCH-58261) showed no clear preference. Radioligand-binding experiments were performed in cells expressing A(2A)R-D(2)R and A(1)R-A(2A)R heteromers to determine possible differences in the affinity of these compounds for different A(2A)R heteromers. Heteromerization played a key role in the presynaptic profile of SCH-442416, since it bound with much less affinity to A(2A)R when co-expressed with D(2)R than with A(1)R. KW-6002 showed the best relative affinity for A(2A)R co-expressed with D(2)R than co-expressed with A(1)R, which can at least partially explain the postsynaptic profile of this compound. Also, the in vitro pharmacological profile of MSX-2, SCH-420814, ZM-241385 and SCH-58261 was is in accordance with their mixed pre- and postsynaptic profile. On the basis of their preferential pre- versus postsynaptic actions, SCH-442416 and KW-6002 may be used as lead compounds to obtain more effective antidyskinetic and antiparkinsonian compounds, respectively. 相似文献
125.
Sotillo J Valero ML Sánchez del Pino MM Fried B Esteban JG Marcilla A Toledo R 《Experimental parasitology》2011,(2):133-137
The somatic extract of Zygocotyle lunata (Trematoda: Paramphistomidae) adults collected from experimentally infected mice was investigated using a proteomic approach to separate and identify tryptic peptides from the somatic extract of Z. lunata adult worms. A shot-gun liquid chromatography/tandem mass spectrometry procedure was used. We used the MASCOT search engine (Matrix-Science) and ProteinPilot software v2.0 (Applied Biosystems) for the database search. A total of 36 proteins were accurately identified from the worms. The largest protein family consisted of metabolic enzymes. Structural, motor and receptor binding proteins and proteins related to oxygen transport were identified in the somatic extract of Z. lunata. This is the first study that attempts to identify the proteome of Z. lunata. However, more work is needed to improve our knowledge of trematodiasis in general and more specifically to have a better understanding about host–parasite relationships in infections with paramphistomes. 相似文献
126.
Wills M Akbar A Beswick M Bosch JA Caruso C Colonna-Romano G Dutta A Franceschi C Fulop T Gkrania-Klotsas E Goronzy J Griffiths SJ Henson S Herndler-Brandstetter D Hill A Kern F Klenerman P Macallan D Macualay R Maier AB Mason G Melzer D Morgan M Moss P Nikolich-Zugich J Pachnio A Riddell N Roberts R Sansoni P Sauce D Sinclair J Solana R Strindhall J Trzonkowski P van Lier R Vescovini R Wang G Westendorp R Pawelec G 《Immunity & ageing : I & A》2011,8(1):10-8
The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vaccination. This commentary summarizes the major findings of these presentations and references subsequently published work from the presenter laboratory where appropriate and draws together major themes that were subsequently discussed along with new areas of interest that were highlighted by this discussion. 相似文献
127.
Biedendieck R Beine R Gamer M Jordan E Buchholz K Seibel J Dijkhuizen L Malten M Jahn D 《Applied microbiology and biotechnology》2007,74(5):1062-1073
Fructosyltransferases, like the Lactobacillus reteri levansucrase, are important for the production of new fructosyloligosaccharides. Various His6- and Strep-tagged variants of this enzyme were recombinantly produced and exported into the growth medium using the Gram-positive
bacterium Bacillus megaterium. Nutrient-rich growth medium significantly enhanced levansucrase production and export. The B. megaterium signal peptide of the extracellular esterase LipA mediated better levansucrase export compared to the one of the penicillin
amidase Pac. The combination of protein export via the LipA signal peptide with the coexpression of the signal peptidase gene
sipM further increased the levansucrase secretion. Fused affinity tags allowed the efficient one-step purification of the recombinant
proteins from the growth medium. However, fused peptide tags led to slightly decreased secretion of tested fusion proteins.
After upscaling 2 to 3 mg affinity tagged levansucrase per liter culture medium was produced and exported. Up to 1 mg of His6-tagged and 0.7 mg of Strep-tagged levansucrase per liter were recovered by affinity chromatography. Finally, the purified
levansucrase was shown to synthesize new fructosyloligosaccharides from the novel donor substrates d-Gal-Fru, d-Xyl-Fru, d-Man-Fru, and d-Fuc-Fru.
R. Biedendieck and R. Beine contributed equally to this work. 相似文献
128.
Maria Cristina Da Silva Cortinhas Chirlei Glienke Alberto José Prioli Rafael Bueno Noleto Daniele Aparecida Matoso Marta Margarete Cestari 《Acta zoologica》2010,91(2):242-248
Da Silva Cortinhas, M. C., Glienke, C., Prioli, A. J., Noleto, R. B., Matoso, D. A. and Cestari, M. M. 2010. A prime inference on genetic diversity (RAPDs) in the marine fish Atherinella brasiliensis (Teleostei, Atherinopsidae) from Southern Brazil. —Acta Zoologica (Stockholm) 91 : 242–248 As a result of the importance of Atherinella brasiliensis in estuarine environments, random amplified polymorphic DNA (RAPD) markers were used to verify the genetic diversity in A. brasiliensis from two different places in Paranaguá Bay (Paraná State) and one from the Conceição Lagoon (Santa Catarina State). Cytogenetic data have shown a high karyotypic diversity in some populations, although in others this peculiarity demonstrates rearrangements such as heterochromatinization. In the present study, a low level of genetic structuring between the samples from Conceição Lagoon compared with the others was observed through principal coordinate analysis (PCO), analysis of molecular variance and Mantel test according to 79 RAPD markers. As this specie does not perform horizontal migration and the individuals of Conceição Lagoon are isolated, three hypotheses are proposed to explain the results: (i) similar environments may show homogeneous populations not depending on the geographical distance, (ii) because vicariant events that formed the bays occurred in a recent period, the fragmentation effects over the structuring of the genetic diversity may still be low and not totally detectable by the RAPD technique and (iii) the isolation time or the number of generations may not be enough to promote a possible differentiation and genetic structuring between the specimens of these three places. The specimens of these places present a low level of differentiation and genetic structuring so we can consider them as a unique homogeneous population. 相似文献
129.
Constanze Bickelmann Rafael Jiménez Michael K. Richardson Marcelo R. Sánchez‐Villagra 《Acta zoologica》2014,95(3):283-289
The humerus of fossorial moles has a highly derived anatomy, reflecting the ecological specialization of these animals for digging. It is short and broad, with enlarged muscle attachment sites and pronounced articulations compared to non‐fossorial sister taxa and other mammals. Both condyles are rotated in opposite directions, resulting in a torsion which is unique among eutherian mammals. The development of this exceptional bone was studied in embryonic stages of the fossorial Iberian mole (Talpa occidentalis) from mesenchymal condensation to incipient ossification based on histological serial sections using 3D reconstruction methods. For comparison, embryonic stages of the semi‐fossorial Japanese shrew mole (Urotrichus talpoides) as well as a sister taxon of moles, the terrestrial North American least shrew (Cryptotis parva), were studied. Results show that the humerus of Talpa already shows its derived anatomy with broadened muscle attachment sites and distinct articulations at early cartilaginous stages, when ossification has just started in the mid‐diaphyseal region. The torsion takes place simultaneously with the medial rotation of the forelimbs. The supracondylar foramen is closed in all studied Talpa embryos, but patent in Cryptotis and Urotrichus. This is an example of developmental penetrance, suggesting that variation of adult elements can be found at early stages as well. 相似文献
130.
Ajith?R?Vancha Suman?Govindaraju Kishore?VL?Parsa Madhuri?Jasti Maribel?González-García Rafael?P?BallesteroEmail author 《BMC biotechnology》2004,4(1):23