全文获取类型
收费全文 | 6048篇 |
免费 | 516篇 |
国内免费 | 1篇 |
出版年
2023年 | 46篇 |
2022年 | 44篇 |
2021年 | 182篇 |
2020年 | 132篇 |
2019年 | 165篇 |
2018年 | 185篇 |
2017年 | 178篇 |
2016年 | 233篇 |
2015年 | 309篇 |
2014年 | 358篇 |
2013年 | 421篇 |
2012年 | 514篇 |
2011年 | 452篇 |
2010年 | 279篇 |
2009年 | 277篇 |
2008年 | 320篇 |
2007年 | 331篇 |
2006年 | 261篇 |
2005年 | 255篇 |
2004年 | 252篇 |
2003年 | 187篇 |
2002年 | 210篇 |
2001年 | 99篇 |
2000年 | 80篇 |
1999年 | 89篇 |
1998年 | 57篇 |
1997年 | 66篇 |
1996年 | 44篇 |
1995年 | 42篇 |
1994年 | 31篇 |
1993年 | 29篇 |
1992年 | 36篇 |
1991年 | 46篇 |
1990年 | 46篇 |
1989年 | 31篇 |
1988年 | 31篇 |
1987年 | 32篇 |
1986年 | 24篇 |
1985年 | 27篇 |
1984年 | 20篇 |
1983年 | 10篇 |
1982年 | 11篇 |
1981年 | 15篇 |
1980年 | 9篇 |
1979年 | 7篇 |
1978年 | 11篇 |
1977年 | 16篇 |
1976年 | 8篇 |
1974年 | 14篇 |
1973年 | 8篇 |
排序方式: 共有6565条查询结果,搜索用时 562 毫秒
1.
2.
Nataly Mancette Rijensky Netta R. Blondheim Shraga Eilon Barnea Nir Peled Eli Rosenbaum Aron Popovtzer Solomon M. Stemmer Alejandro Livoff Mark Shlapobersky Neta Moskovits Dafna Perry Eitan Rubin Itzhak Haviv Arie Admon 《Molecular & cellular proteomics : MCP》2020,19(8):1360-1374
Highlights
- •Sufficient tumor tissues are often unavailable large HLA peptidome discovery.
- •Using patient derived xenograft (PDX) tumors can overcome this limitation.
- •The large PDX HLA peptidomes expand significantly those of the original biopsies.
- •The HLA peptidomes of the PDX tumors included many tumor antigens.
3.
4.
A pertussis toxin-sensitive G-protein mediates some aspects of insulin action in BC3H-1 murine myocytes. 总被引:9,自引:0,他引:9
L Luttrell E Kilgour J Larner G Romero 《The Journal of biological chemistry》1990,265(28):16873-16879
The involvement of G-proteins in the insulin signal transduction system has been studied in detail using the murine BC3H-1 myocyte system. Pertussis toxin (PT) treatment, previously shown to attenuate some of the metabolic effects of insulin in this cell line (Luttrell, L.M., Hewlett, E.L., Romero, G., and Rogol, A.D. (1988) J. Biol. Chem. 263, 6134-6141), abolished insulin-induced generation of diacylglycerol and inositolglycan mediators with no effects on either the autophosphorylation of the insulin receptor or the phosphorylation of the major endogenous substrates for insulin-stimulated tyrosine kinase activity (pp185 and pp42-45). In vitro ADP-ribosylation and immunoblotting studies suggest that the major PT substrate is a 40-kDa protein of the G alpha family. This protein band did not exhibit detectable tyrosine phosphorylation upon stimulation of either intact cells or cell membranes with insulin. In the presence of low concentrations of GTP, insulin treatment of isolated myocyte plasma membranes resulted in a small (30-40%) but significant stimulation of GTP hydrolysis. This effect was best observed in the presence of small concentrations of sodium dodecyl sulfate. The rate of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) binding to BC3H-1 membranes was also significantly increased in the presence of insulin. The effects of insulin on GTP hydrolysis and GTP gamma S binding were found to be dependent on the concentration of insulin. These effects were not detected in plasma membranes prepared from PT-pretreated BC3H-1 myocytes. In contrast, pretreatment with the B (inactive) subunit of PT did not alter the response of myocyte membranes to insulin. High affinity binding of [125I]iodoinsulin to myocyte plasma membranes was reduced by 60-70% in the presence of guanine nucleotides. Similar effects on insulin binding were produced by PT pretreatment of the cells. In contrast, adenine nucleotides had no effect on insulin binding. Scatchard analysis of the binding data showed that the observed effects of guanine nucleotides and PT on insulin binding resulted either from a reduction in the number of high affinity insulin binding sites or from a significant reduction of the affinity of insulin for its receptor. Low affinity binding sites did not appear to be affected by either guanine nucleotides nor PT pretreatment. These results provide substantial evidence suggestive of a noncovalent interaction between the insulin receptor and a regulatory G-protein system during the process of insulin signaling. 相似文献
5.
Carles Grau Romuald Ginhoux Alejandro Riera Thanh Lam Nguyen Hubert Chauvat Michel Berg Julià L. Amengual Alvaro Pascual-Leone Giulio Ruffini 《PloS one》2014,9(8)
Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI) has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI). These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B) communication between subjects (hyperinteraction). Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG) changes with a CBI inducing the conscious perception of phosphenes (light flashes) through neuronavigated, robotized transcranial magnetic stimulation (TMS), with special care taken to block sensory (tactile, visual or auditory) cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues. 相似文献
6.
Mutations in the human homolog of the Vhlh gene [encoding the von-Hippel Lindau (VHL) protein] lead to tumor development. In mice, depletion of Vhlh in pancreatic ß-cells causes perturbed glucose homeostasis, but the role of this gene in other pancreatic cells is poorly understood. To investigate the function of VHL/HIF pathway in pancreatic cells, we inactivated Vhlh in the pancreatic epithelium as well as in the endocrine and exocrine lineages. Our results show that embryonic depletion of Vhlh within the pancreatic epithelium causes postnatal lethality due to severe hypoglycemia. The hypoglycemia is recapitulated in mice with endocrine-specific removal of Vhlh, while animals with loss of Vhlh predominantly in the exocrine compartment survive to adulthood with no overt defects in glucose metabolism. Mice with hypoglycemia display diminished insulin release in response to elevated glucose. Significantly, the glucagon response is impaired both in vivo (circulating glucagon levels) as well as in an in vitro secretion assay in isolated islets. Hypoxia also impairs glucagon secretion in a glucagon-expressing cell line in culture. Our results reveal a novel role for the hypoxia/HIF pathway in islet hormone secretion and maintenance of the fine balance that allows for the establishment of normoglycemia. 相似文献
7.
María Sitges† Lourival Domingos Possani‡ Alejandro Bayón† 《Journal of neurochemistry》1987,48(6):1745-1752
Toxic peptides II-9.2.2 and II-10, purified from Centruroides noxius venom, bear highly homologous N-terminal amino acid sequences, and both toxins are lethal to mice. However, only toxin II-10 is active on the voltage-clamped squid axon, selectively decreasing the voltage-dependent Na+ current. Here, we have tested toxins II-9 and II-10 on synaptosomes from mouse brain: both toxins increased the release of gamma-[3H]aminobutyric acid ([3H]GABA). Their effect was completely blocked by tetrodotoxin or by the absence of external Na+. Also, both toxins increased Na+ permeability in isolated nerve terminals. Besides the observation that toxin II-9 is active on synaptosomes, the effect of toxin II-10 in this preparation is opposite to that observed in the squid axon. Thus, our results reflect functional differences between the populations of Na+ channels in mouse brain synaptosomes and in the squid axon. The release of GABA evoked by these toxins from synaptosomes required external Ca2+ and was blocked by Ca2+ channel blockers (verapamil and Co2+). This latter observation is in sharp contrast to the releasing action of veratrine, which evoked release even in the absence of external Ca2+. Furthermore, the action of both C. noxius toxins was potentiated by veratrine, a result suggesting they have different mechanisms of action. Among drugs that release neurotransmitters by increasing Na+ permeability, it is noteworthy that scorpion toxins are the only ones yet reported to have a strict requirement for external Ca2+. 相似文献
8.
Intracellular accumulation of nitrate, indicative of the operation of an active nitrate transport system, has been measured in intact cells of the cyanobacterium Anacystis nidulans. The ability of the cells to accumulate nitrate was effectively hindered by either ammonium addition or selective inhibition of CO2 fixation by DL-glyceraldehyde, with the effect of either compound being prevented by previously blocking ammonium assimilation. The results support the contention that nitrate utilization in cyanobacteria is regulated at the level of nitrate transport through the concerted action of ammonium assimilation and CO2 fixation. 相似文献
9.
M M Almar J Díaz-Mayans F J Romero 《Comp. Biochem. Physiol. C, Comp. Pharmacol. Toxicol.》1987,87(2):433-435
1. Glutathione content and GSH S-transferase activity in the midgut gland of Procambarus clarkii (P. c.) of different sex and body weight are presented. 2. Procambarus clarkii females' GSH concentration in the midgut gland decreases to a higher extent upon fasting, compared with males. 3. Procambarus clarkii females, both in control and fasting conditions, have a slightly higher GSH S-transferase activity than males. 4. Cadmium present in water only affects GSH content and GSH S-transferase activity (after 96 hr) in midgut gland, with cadmium chloride concentrations higher than 100 micrograms/l. 相似文献
10.
Robert L. Brownell Jr. Lloyd T. Findley Omar Vidal Alejandro Robles Silvia Manzanilla N 《Marine Mammal Science》1987,3(1):22-30
The vaquita, Phocoena sinus , is a porpoise in the family Phocoenidae that lives only in the Gulf of California. The external appearance of P. sinus was unknown until 13 fresh specimens were recently examined. The most obvious morphological feature distinguishing P. sinus from its two congeners is the proportionately higher dorsal fin. The most striking features of the pigmentation pattern are the large black eye patches and the black upper and lower lip patches. In both areas, the pigmentation contrasts sharply with the surrounding light gray coloration. The total lengths of the specimens ranged from 70.3 cm (a neonate) to 143.5 cm (an adult female). 相似文献