全文获取类型
收费全文 | 1641篇 |
免费 | 137篇 |
国内免费 | 1篇 |
专业分类
1779篇 |
出版年
2023年 | 7篇 |
2022年 | 12篇 |
2021年 | 25篇 |
2020年 | 16篇 |
2019年 | 28篇 |
2018年 | 25篇 |
2017年 | 22篇 |
2016年 | 41篇 |
2015年 | 67篇 |
2014年 | 72篇 |
2013年 | 86篇 |
2012年 | 124篇 |
2011年 | 138篇 |
2010年 | 66篇 |
2009年 | 57篇 |
2008年 | 105篇 |
2007年 | 105篇 |
2006年 | 94篇 |
2005年 | 105篇 |
2004年 | 96篇 |
2003年 | 83篇 |
2002年 | 87篇 |
2001年 | 16篇 |
2000年 | 20篇 |
1999年 | 17篇 |
1998年 | 25篇 |
1997年 | 18篇 |
1996年 | 4篇 |
1995年 | 11篇 |
1994年 | 16篇 |
1993年 | 17篇 |
1992年 | 11篇 |
1991年 | 6篇 |
1990年 | 9篇 |
1989年 | 9篇 |
1988年 | 12篇 |
1987年 | 19篇 |
1986年 | 7篇 |
1985年 | 8篇 |
1984年 | 11篇 |
1983年 | 5篇 |
1982年 | 10篇 |
1981年 | 11篇 |
1980年 | 7篇 |
1978年 | 6篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1974年 | 4篇 |
1973年 | 7篇 |
1940年 | 6篇 |
排序方式: 共有1779条查询结果,搜索用时 15 毫秒
91.
Huppert FA Baylis N 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2004,359(1449):1447-1451
Well-being: towards an integration of psychology, neurobiology and social science 相似文献
92.
Goubaeva F Ghosh M Malik S Yang J Hinkle PM Griendling KK Neubig RR Smrcka AV 《The Journal of biological chemistry》2003,278(22):19634-19641
We previously developed peptides that bind to G protein betagamma subunits and selectively block interactions between betagamma subunits and a subset of effectors in vitro (Scott, J. K., Huang, S. F., Gangadhar, B. P., Samoriski, G. M., Clapp, P., Gross, R. A., Taussig, R., and Smrcka, A. V. (2001) EMBO J. 20, 767-776). Here, we created cell-permeating versions of some of these peptides by N-terminal modification with either myristate or the cell permeation sequence from human immunodeficiency virus TAT protein. The myristoylated betagamma-binding peptide (mSIRK) applied to primary rat arterial smooth muscle cells caused rapid activation of extracellular signal-regulated kinase 1/2 in the absence of an agonist. This activation did not occur if the peptide lacked a myristate at the N terminus, if the peptide had a single point mutation to eliminate betagamma subunit binding, or if the cells stably expressed the C terminus of betaARK1. A human immunodeficiency virus TAT-modified peptide (TAT-SIRK) and a myristoylated version of a second peptide (mSCAR) that binds to the same site on betagamma subunits as mSIRK, also caused extracellular signal-regulated kinase activation. mSIRK also stimulated Jun N-terminal kinase phosphorylation, p38 mitogen-activated protein kinase phosphorylation, and phospholipase C activity and caused Ca2+ release from internal stores. When tested with purified G protein subunits in vitro, SIRK promoted alpha subunit dissociation from betagamma subunits without stimulating nucleotide exchange. These data suggest a novel mechanism by which selective betagamma-binding peptides can release G protein betagamma subunits from heterotrimers to stimulate G protein pathways in cells. 相似文献
93.
Translation initiation, the rate-limiting step in protein synthesis, is a key event in vascular smooth muscle cell growth, a major component of vascular disease. Translation initiation is regulated by interaction between PHAS-I and the eukaryotic initiation factor 4E (eIF4E). Although angiotensin II (Ang II)-induced vascular smooth muscle cell hypertrophy requires the generation of reactive oxygen species (ROS), the ROS sensitivity of these events and their upstream activators remain unclear. Here, we investigated the role of ROS in the regulation of PHAS-I phosphorylation on Thr-70 and Ser-65, an event required for the release of eIF4E from PHAS-I. Ang II-induced Ser-65 phosphorylation was ROS-dependent as assessed by pretreatment with ebselen (3.6 +/- 0.2 versus 1.1 +/- 0.2), diphenylene iodonium (3.6 +/- 0.2 versus 1.0 +/- 0.1), and N-acetyl cysteine (3.6 +/- 0.2 versus 1.2 +/- 0.1), but Ang II-stimulated phosphorylation of Thr-70 was ROS-insensitive. Although phosphatidylinositol 3-kinase pathway inhibition by LY294004 blocked both Ser-65 and Thr-70 phosphorylation (3.8 +/- 0.1 versus 0.8 +/- 0.1 and 3.2 +/- 0.2 versus 1.0 +/- 0.01, respectively), protein phosphatase 2A inhibition by okadaic acid selectively increased (3.3 +/- 0.1 versus 5.2 +/- 0.1) and p38 mitogen-activated protein kinase inhibition by SB203580 selectively decreased (3.8 +/- 0.1 versus 1.4 +/- 0.3) Ser-65 phosphorylation. Dominant negative Akt adenovirus also inhibited only Ser-65 phosphorylation (3.7 +/- 0.1 versus 1.0 +/- 0.03). These results demonstrate a unique differential ROS sensitivity of two separate residues on PHAS-I, which seems to be explained by the selective involvement of distinct signaling pathways in the regulation of these phosphorylation events. 相似文献
94.
Zhang M Crocker RL Mankin RW Flanders KL Brandhorst-Hubbard JL 《Journal of economic entomology》2003,96(6):1704-1710
Activity patterns of Phyllophaga crinita (Burmeister), Phyllophaga congrua (LeConte), Phyllophaga crassissima (Blanchard), and Cyclocephala lurida (Bland) grubs were monitored with acoustic sensors in small pots of bluegrass, Poa arachnifera Torr, at varying and constant temperatures over multiple-day periods. Experienced listeners readily distinguished three types of sound with distinct differences in frequency and temporal patterns, intensities, and durations. Of approximately 3,000 sounds detected from P. crinita larvae, 7% were identifiable as snaps, with large amplitudes and short durations typically associated with root breakage or clipping activity. Approximately 60% were identifiable as rustles, suggestive of surfaces sliding or rubbing past each other during general movement activity. Another 2% of sounds contained patterns of repeated pulses suggestive of surfaces scraping across a pointed ridge. The remaining 31% had spectral or temporal patterns that fell outside the ranges of easily recognizable sound types. Because the behavioral significance of the different sound types has not yet been fully established, the classified and unclassified sounds were pooled together in analyses of the effects of species, temperature, weight, and time of day. Grubs of all four species produced detectable sounds at rates that increased with temperature [0.45 sounds/((min)(degrees C))] and larval weight [6.3 sounds/((min)(g))]. Mean sound rates were independent of species and time of day. At temperatures <9 degrees C, mean sound rates fell below the typical levels of background noise observed under field conditions. This reduced activity at low temperatures is likely to reduce the effectiveness of acoustic monitoring in the field in cold weather. The consistency of results obtained in these tests over multiple-day periods suggests that acoustic systems have potential as tools for nondestructive monitoring of the efficacy of insect management treatments as well as for biological and ecological studies. 相似文献
95.
Measuring dynamics of caspase-8 activation in a single living HeLa cell during TNFalpha-induced apoptosis 总被引:4,自引:0,他引:4
In this study, we reported the first measurement of the dynamics of activation of caspase-8 in a single living cell. This measurement was conducted using a specially developed molecular sensor based on the FRET (fluorescence resonance energy transfer) technique. This sensor was constructed by fusing a CFP (cyan fluorescent protein) and a YFP (yellow fluorescent protein) with a linker containing a tandem caspase-8-specific cleavage site. The change of the FRET ratio upon cleavage was larger than 4-fold. Using this sensor, we found that during TNFalpha-induced apoptosis, the activation of caspase-8 was a slower process than that of caspase-3, and it was initiated much earlier than the caspase-3 activation. Inhibition of caspase-9 delayed the full activation of caspase-3 but did not affect the dynamics of caspase-8. Results of these single-cell measurements suggested that caspase-3 was activated by caspase-8 through two parallel pathways during TNFalpha-induced apoptosis in HeLa cells. 相似文献
96.
A receptor linked to a Gi-family G-protein functions in initiating oocyte maturation in starfish but not frogs 总被引:1,自引:0,他引:1
The stimulation of oocyte maturation by 1-methyladenine in starfish, and by a steroid in frogs, has been proposed to involve G-protein-coupled receptors. To examine whether activation of receptors linked to G(i) or G(z) was sufficient to cause oocyte maturation, we expressed mammalian G(i)- and G(z)-linked receptors in starfish and frog oocytes. Application of the corresponding agonists caused meiosis to resume in the starfish but not the frog oocytes. We confirmed that the receptors were effectively expressed in the frog oocytes by using a chimeric G-protein, G(qi), that converts input from G(i)- and G(z)-linked receptors to a G(q) output and results in a contraction of the oocyte's pigment. These results argue against G(i) or G(z) functioning to cause maturation in frog oocytes. Consistently, maturation-inducing steroids did not cause pigment contraction in frog oocytes expressing G(qi), and G(z) protein was not detectable in frog oocytes. For starfish oocytes, however, our results support the conclusion that G(i) functions in 1-methyladenine signaling and suggest the possibility of using frog oocyte pigment contraction as an assay to identify the 1-methyladenine receptor. To test this concept, we coexpressed G(qi) and a starfish adenosine receptor in frog oocytes and showed that applying adenosine caused pigment contraction. 相似文献
97.
NF-kappaB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4 总被引:34,自引:0,他引:34
Helbig G Christopherson KW Bhat-Nakshatri P Kumar S Kishimoto H Miller KD Broxmeyer HE Nakshatri H 《The Journal of biological chemistry》2003,278(24):21631-21638
98.
Selznick SH Thatcher ML Brown KS Haussler CA 《In vitro cellular & developmental biology. Animal》2001,37(1):55-61
Prototype computer software for a Cell Culture Laboratory Management System (CCLMS) has been developed to relieve cell culture specialists of the burden of manual recordkeeping. Conventional data archives in cell culture laboratories are prone to error and expensive to maintain. The reliance upon cell culture to provide models for biochemical and molecular biological research serves to magnify errors at great expense. The CCLMS prototype encapsulates a modular software application that manages the many aspects of cell culture laboratory recordkeeping. A transaction-based database stores detailed information on subcultures, freezes and thaws, prints waterproof labels for culture vessels, and provides for immediate historical trace-back of any cultured cell line. Linked database files store information specific to an individual culture flask while removing redundancy between similar groups of flasks. A frozen cell log maintains locations of all vials within any type of cryogenic storage unit, locates spaces for newly frozen cell lines, and generates alphabetical or numerical reports. Finally, modules for maintaining cell counts, user records, and culture vessel specifications to support a comprehensive automation process are incorporated within this software. The developed CCLMS prototype has been demonstrated to be an adaptable, reliable tool for improving training, efficiency, and historical rigor for two independent cell culture facilities. 相似文献
99.
Carlin Ryan W.; Quesnell Rebecca R.; Zheng Ling; Mitchell Kathy E.; Schultz Bruce D. 《American journal of physiology. Cell physiology》2002,283(4):C1033
This study focused on the role ofsodium-bicarbonate cotransporter (NBC1) in cAMP-stimulated iontransport in porcine vas deferens epithelium. Ion substitutionexperiments in modified Ussing chambers revealed that cAMP-mediatedstimulation was dependent on the presence of Na+,HCO , and Cl for a full response.HCO -dependent current was unaffected byacetazolamide, bumetanide, or amiloride but was inhibited bybasolateral 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid.Na+-driven, HCO -dependent,stilbene-inhibitable anion flux was observed across the basolateralmembrane of selectively permeabilized monolayers. Results ofradiotracer flux studies suggest a4,4'-dinitrostilbene-2,2'-disulfonate-sensitive stoichiometry of 2 baseequivalents per Na+. Antibodies raised against rat kidneyNBC epitopes (rkNBC; amino acids 338-391 and 928-1035)identified a single band of ~145 kDa. RT-PCR detected NBC1 message inporcine vas deferens epithelia. These results demonstrate that vasdeferens epithelial cells possess the proteins necessary for thevectoral transport of HCO and that these mechanismsare maintained in primary culture. Taken together, the results indicatethat vas deferens epithelia play an active role in male fertility andhave implications for our understanding of the relationship betweencystic fibrosis and congenital bilateral absence of the vas deferens. 相似文献
100.
Two genetic circuits repress the Caenorhabditis elegans heterochronic gene lin-28 after translation initiation 总被引:14,自引:0,他引:14
The heterochronic gene lin-28 of the nematode Caenorhabditis elegans controls the relative timing of diverse developmental events during the animal's larval stages. lin-28 is stage-specifically regulated by two genetic circuits: negatively by the 22-nt RNA lin-4 and positively by the heterochronic gene lin-14. Here, we show that lin-28 is repressed during normal development by a mechanism that acts on its mRNA after translation initiation. We provide evidence that lin-14 inhibits a negative regulation that is independent of the lin-4 RNA and involves the gene daf-12, which encodes a nuclear hormone receptor. The lin-4-independent repression does not affect the initiation of translation on the lin-28 mRNA, and like the lin-4-mediated repression, acts through the gene's 3'-untranslated region. In addition, we find that lin-4 is not sufficient to cause repression of lin-28 if the lin-4-independent circuit is inhibited. Therefore, the lin-4-independent circuit likely contributes substantially to the down-regulation of lin-28 that occurs during normal development. The role of lin-4 may be to initiate or potentiate the lin-4-independent circuit. We speculate that a parallel lin-4-independent regulatory mechanism regulates the expression of lin-14. 相似文献