全文获取类型
收费全文 | 3785篇 |
免费 | 370篇 |
国内免费 | 2篇 |
专业分类
4157篇 |
出版年
2023年 | 32篇 |
2022年 | 45篇 |
2021年 | 94篇 |
2020年 | 64篇 |
2019年 | 46篇 |
2018年 | 57篇 |
2017年 | 73篇 |
2016年 | 122篇 |
2015年 | 221篇 |
2014年 | 228篇 |
2013年 | 222篇 |
2012年 | 314篇 |
2011年 | 287篇 |
2010年 | 178篇 |
2009年 | 178篇 |
2008年 | 246篇 |
2007年 | 200篇 |
2006年 | 198篇 |
2005年 | 204篇 |
2004年 | 176篇 |
2003年 | 178篇 |
2002年 | 164篇 |
2001年 | 30篇 |
2000年 | 31篇 |
1999年 | 30篇 |
1998年 | 51篇 |
1997年 | 34篇 |
1996年 | 26篇 |
1995年 | 29篇 |
1994年 | 22篇 |
1993年 | 21篇 |
1992年 | 21篇 |
1991年 | 16篇 |
1990年 | 18篇 |
1989年 | 12篇 |
1988年 | 14篇 |
1987年 | 13篇 |
1984年 | 19篇 |
1983年 | 12篇 |
1981年 | 25篇 |
1980年 | 12篇 |
1979年 | 16篇 |
1978年 | 10篇 |
1977年 | 19篇 |
1976年 | 10篇 |
1974年 | 8篇 |
1973年 | 12篇 |
1970年 | 9篇 |
1969年 | 8篇 |
1968年 | 10篇 |
排序方式: 共有4157条查询结果,搜索用时 15 毫秒
81.
Louise Rosson 《New Zealand journal of zoology.》2013,40(4):267-269
Abstract The Otago Regional Council could perhaps be renamed the Otago Rabbit Council. Some 35% of our budget—$8 million—goes annually towards dealing with rabbits, which certainly meet the definition of a pest (an animal which “disrupts management objectives” and lives at a population density exceeding “what society considers to be an acceptable level”). We can only hope that the day will come when we can, with confidence, say that the problem is being solved and when public and private financial inputs into rabbit control can be set at a far more reasonable level. 相似文献
82.
Zoe Barclay Louise Dickson Derek Robertson Melanie Johnson Pamela Holland Roberta Rosie Liting Sun Helen Jerina Eve Lutz Sue Fleetwood-Walker Rory Mitchell 《Cellular signalling》2013,25(4):814-821
The 5-HT2A receptor (5-HT2AR) is implicated in psychotropic changes within the central nervous system (CNS). A number of polymorphisms have been reported in the 5-HT2AR gene; one of these results in a non-synonymous change, H452Y, in the carboxy-terminal tail of the receptor protein. The minor allele (9% occurrence) has been statistically associated with CNS dysfunction such as impaired memory processing and resistance to neuroleptic treatment in schizophrenic patients. We investigated the impact of H452Y mutation of the 5-HT2AR expressed in COS7 cells on distinctly coupled intracellular signalling pathways from the receptor, focusing on the heterotrimeric G protein-independent phospholipase D (PLD) pathway, compared to the conventional Gq/11-linked phospholipase C (PLC) pathway. The H452Y mutation selectively attenuated PLD signalling, which as in the wild-type receptor, was mediated by a molecular complex involving PLD1 docked to the receptor's carboxy-terminal tail domain. Co-immunoprecipitation and GST-fusion protein experiments revealed that the H452Y mutation selectively reduced PLD1 binding to the receptor. Experiments with blocking peptides to mimic short sections of the 5-HT2AR tail sequence revealed that the peptide spanning residue 452 strongly reduced PLD but not PLC responses of the receptor. Similar observations were made when assessing both PLD responses and PLD-dependent cellular proliferation elicited by activation of 5-HT2ARs natively expressed in MCF-7 cells. Overall these findings indicate that the H452Y polymorphic variant of the 5-HT2AR displays selective disruption of its PLD signalling pathway. This may potentially play a role in the CNS dysfunction associated with the H452Y allele of the 5-HT2AR. 相似文献
83.
84.
Louise Vincent 《Ethnic and racial studies》2013,36(8):1426-1451
This paper argues that, while the demise of apartheid has led to many situations in which South Africans now come into closer contact with one another, this increased ‘contact’ does not amount to greater racial integration. Contact occurs within a context of unequal power relations in which ‘whiteness’ continues to be privileged over ‘blackness’. The result is that white people tend to benefit more from contact with the racial ‘other’ than black people, who often experience this contact as reinforcing their expectations of continued white dominance and privilege. While contact may undermine blatantly racist practices and overt racial conflict, racialized patterns of reasoning continue to exist, often unnoticed and unchallenged. These include the assumption that race is an incontrovertible fact of experience, the privileging of whiteness, the assumption that there exist different (biological) races which evince different forms of social behaviour and that these are essential properties of people rather than being historically or socially contingent. 相似文献
85.
Louise E. Kemp Marion Rusch Alexander Adibekian Hayley E. Bullen Arnault Graindorge Céline Freymond Matthias Rottmann Catherine Braun-Breton Stefan Baumeister Arthur T. Porfetye Ingrid R. Vetter Christian Hedberg Dominique Soldati-Favre 《The Journal of biological chemistry》2013,288(38):27002-27018
In eukaryotic organisms, cysteine palmitoylation is an important reversible modification that impacts protein targeting, folding, stability, and interactions with partners. Evidence suggests that protein palmitoylation contributes to key biological processes in Apicomplexa with the recent palmitome of the malaria parasite Plasmodium falciparum reporting over 400 substrates that are modified with palmitate by a broad range of protein S-acyl transferases. Dynamic palmitoylation cycles require the action of an acyl-protein thioesterase (APT) that cleaves palmitate from substrates and conveys reversibility to this posttranslational modification. In this work, we identified candidates for APT activity in Toxoplasma gondii. Treatment of parasites with low micromolar concentrations of β-lactone- or triazole urea-based inhibitors that target human APT1 showed varied detrimental effects at multiple steps of the parasite lytic cycle. The use of an activity-based probe in combination with these inhibitors revealed the existence of several serine hydrolases that are targeted by APT1 inhibitors. The active serine hydrolase, TgASH1, identified as the homologue closest to human APT1 and APT2, was characterized further. Biochemical analysis of TgASH1 indicated that this enzyme cleaves substrates with a specificity similar to APTs, and homology modeling points toward an APT-like enzyme. TgASH1 is dispensable for parasite survival, which indicates that the severe effects observed with the β-lactone inhibitors are caused by the inhibition of non-TgASH1 targets. Other ASH candidates for APT activity were functionally characterized, and one of them was found to be resistant to gene disruption due to the potential essential nature of the protein. 相似文献
86.
Christophe Blanchetot Dennis Verzijl Azra Muji?-Deli? Leontien Bosch Louise Rem Rob Leurs C. Theo Verrips Michael Saunders Hans de Haard Martine J. Smit 《The Journal of biological chemistry》2013,288(35):25173-25182
Chemokine receptors and their ligands play a prominent role in immune regulation but many have also been implicated in inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, allograft rejection after transplantation, and also in cancer metastasis. Most approaches to therapeutically target the chemokine system involve targeting of chemokine receptors with low molecular weight antagonists. Here we describe the selection and characterization of an unprecedented large and diverse panel of neutralizing Nanobodies (single domain camelid antibodies fragment) directed against several chemokines. We show that the Nanobodies directed against CCL2 (MCP-1), CCL5 (RANTES), CXCL11 (I-TAC), and CXCL12 (SDF-1α) bind the chemokines with high affinity (at nanomolar concentration), thereby blocking receptor binding, inhibiting chemokine-induced receptor activation as well as chemotaxis. Together, we show that neutralizing Nanobodies can be selected efficiently for effective and specific therapeutic treatment against a wide range of immune and inflammatory diseases. 相似文献
87.
Linking phospholipase C isoforms with differentiation function in human vascular smooth muscle cells
Louise S. Mackenzie Joanne S. Lymn Alun D. Hughes 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2013,1833(12):3006-3012
The phosphoinositol-phospholipase C (PLC) family of enzymes consists of a number of isoforms, each of which has different cellular functions. PLCγ1 is primarily linked to tyrosine kinase transduction pathways, whereas PLCδ1 has been associated with a number of regulatory proteins, including those controlling the cell cycle. Recent studies have shown a central role of PLC in cell organisation and in regulating a wide array of cellular responses. It is of importance to define the precise role of each isoform, and how this changes the functional outcome of the cell. Here we investigated differences in PLC isoform levels and activity in relation to differentiation of human and rat vascular smooth muscle cells. Using Western blotting and PLC activity assay, we show that PLCδ1 and PLCγ1 are the predominant isoforms in randomly cycling human vascular smooth muscle cells (HVSMCs). Growth arrest of HVSMCs for seven days of serum deprivation was consistently associated with increases in PLCδ1 and SM α-actin, whereas there were no changes in PLCγ1 immuno-reactivity. Organ culture of rat mesenteric arteries in serum free media (SFM), a model of de-differentiation, led to a loss of contractility as well as a loss of contractile proteins (SM α-actin and calponin) and PLCδ1, and no change in PLCγ1 immuno-reactivity. Taken together, these data indicate that PLCδ1 is the predominant PLC isoform in vascular smooth muscle, and confirm that PLCδ1 expression is affected by conditions that affect the cell cycle, differentiation status and contractile function. 相似文献
88.
Livestock have been seen either as a source of subsistence or as commodities in a process of capital accumulation. Is the association of cattle with capital just a poetic metaphor or the grounds for a serious analysis of third world herding communities? Economists are divided between an orthodox notion of capital as physical equipment and a Marxist emphasis on social relations dominated by money. Nevertheless, some anthropologists assert that herders should be conceptualised as capitalists. The key elements in the Western folk concept of capital are: increase, money, physical stock and preoccupation with future time. Despite the plausible link between herding and some of these ideas, we conclude that, as an analytical category, ‘capital’ is too loaded and diffuse for fruitful application to the analysis of pastoralist production. 相似文献
89.
Jingyi Zhu Ivo?H.M. van?Stokkum Laura Paparelli Michael?R. Jones Marie?Louise Groot 《Biophysical journal》2013,104(11):2493-2502
A question at the forefront of biophysical sciences is, to what extent do quantum effects and protein conformational changes play a role in processes such as biological sensing and energy conversion? At the heart of photosynthetic energy transduction lie processes involving ultrafast energy and electron transfers among a small number of tetrapyrrole pigments embedded in the interior of a protein. In the purple bacterial reaction center (RC), a highly efficient ultrafast charge separation takes place between a pair of bacteriochlorophylls: an accessory bacteriochlorophyll (B) and bacteriopheophytin (H). In this work, we applied ultrafast spectroscopy in the visible and near-infrared spectral region to Rhodobacter sphaeroides RCs to accurately track the timing of the electron on BA and HA via the appearance of the BA and HA anion bands. We observed an unexpectedly early rise of the HA− band that challenges the accepted simple picture of stepwise electron transfer with 3 ps and 1 ps time constants. The implications for the mechanism of initial charge separation in bacterial RCs are discussed in terms of a possible adiabatic electron transfer step between BA and HA, and the effect of protein conformation on the electron transfer rate. 相似文献
90.
Alyssa D. Flora Louise D. Teel Mark A. Smith James F. Sinclair Angela R. Melton-Celsa Alison D. O’Brien 《PloS one》2013,8(7)
Ricin is a potent toxin found in the beans of Ricinus communis and is often lethal for animals and humans when aerosolized or injected and causes significant morbidity and occasional death when ingested. Ricin has been proposed as a bioweapon because of its lethal properties, environmental stability, and accessibility. In oral intoxication, the process by which the toxin transits across intestinal mucosa is not completely understood. To address this question, we assessed the impact of ricin on the gastrointestinal tract and organs of mice after dissemination of toxin from the gut. We first showed that ricin adhered in a specific pattern to human small bowel intestinal sections, the site within the mouse gut in which a variable degree of damage has been reported by others. We then monitored the movement of ricin across polarized human HCT-8 intestinal monolayers grown in transwell inserts and in HCT-8 cell organoids. We observed that, in both systems, ricin trafficked through the cells without apparent damage until 24 hours post intoxication. We delivered a lethal dose of purified fluorescently-labeled ricin to mice by oral gavage and followed transit of the toxin from the gastrointestinal tracts to the internal organs by in vivo imaging of whole animals over time and ex vivo imaging of organs at various time points. In addition, we harvested organs from unlabeled ricin-gavaged mice and assessed them for the presence of ricin and for histological damage. Finally, we compared serum chemistry values from buffer-treated versus ricin-intoxicated animals. We conclude that ricin transverses human intestinal cells and mouse intestinal cells in situ prior to any indication of enterocyte damage and that ricin rapidly reaches the kidneys of intoxicated mice. We also propose that mice intoxicated orally with ricin likely die from distributive shock. 相似文献