全文获取类型
收费全文 | 2552篇 |
免费 | 197篇 |
专业分类
2749篇 |
出版年
2023年 | 13篇 |
2022年 | 41篇 |
2021年 | 78篇 |
2020年 | 41篇 |
2019年 | 55篇 |
2018年 | 56篇 |
2017年 | 49篇 |
2016年 | 64篇 |
2015年 | 127篇 |
2014年 | 152篇 |
2013年 | 187篇 |
2012年 | 228篇 |
2011年 | 257篇 |
2010年 | 151篇 |
2009年 | 134篇 |
2008年 | 128篇 |
2007年 | 137篇 |
2006年 | 91篇 |
2005年 | 106篇 |
2004年 | 107篇 |
2003年 | 84篇 |
2002年 | 82篇 |
2001年 | 17篇 |
2000年 | 14篇 |
1999年 | 23篇 |
1998年 | 29篇 |
1997年 | 11篇 |
1996年 | 13篇 |
1995年 | 23篇 |
1994年 | 10篇 |
1993年 | 11篇 |
1992年 | 15篇 |
1991年 | 8篇 |
1989年 | 8篇 |
1988年 | 10篇 |
1987年 | 6篇 |
1986年 | 8篇 |
1985年 | 9篇 |
1984年 | 11篇 |
1983年 | 13篇 |
1982年 | 9篇 |
1981年 | 11篇 |
1980年 | 6篇 |
1979年 | 9篇 |
1978年 | 11篇 |
1975年 | 7篇 |
1974年 | 8篇 |
1973年 | 5篇 |
1971年 | 6篇 |
1970年 | 7篇 |
排序方式: 共有2749条查询结果,搜索用时 15 毫秒
141.
Sam Cooper Amine Sadok Vicky Bousgouni Chris Bakal 《Molecular biology of the cell》2015,26(22):4163-4170
Melanoma cells can adopt two functionally distinct forms, amoeboid and mesenchymal, which facilitates their ability to invade and colonize diverse environments during the metastatic process. Using quantitative imaging of single living tumor cells invading three-dimensional collagen matrices, in tandem with unsupervised computational analysis, we found that melanoma cells can switch between amoeboid and mesenchymal forms via two different routes in shape space—an apolar and polar route. We show that whereas particular Rho-family GTPases are required for the morphogenesis of amoeboid and mesenchymal forms, others are required for transitions via the apolar or polar route and not amoeboid or mesenchymal morphogenesis per se. Altering the transition rates between particular routes by depleting Rho-family GTPases can change the morphological heterogeneity of cell populations. The apolar and polar routes may have evolved in order to facilitate conversion between amoeboid and mesenchymal forms, as cells are either searching for, or attracted to, particular migratory cues, respectively. 相似文献
142.
Bryant C. Nelson Joseph J. Dalluge Sam A. Margolis 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2001,765(2):141-150
Liquid chromatography (LC) in direct combination with mass spectrometry (MS) has been shown to be a good analytical technique for the selective separation and detection of labile folate monoglutamates. Reversed-phase LC and electrospray-ionization MS conditions were developed and optimized for the separation and detection of 5-methyltetrahydrofolic acid, 5-formyl tetrahydrofolic acid, tetrahydrofolic acid, dihydrofolic acid and folic acid in aqueous samples. Representative and reproducible positive ion mass spectra were generated for each folate under mild MS conditions. The selective MS detection and identification of endogenous 5-methyltetrahydrofolic acid in human plasma was accomplished through the development of a straightforward C18-based solid-phase extraction procedure. This procedure allows for the qualitative assessment of 5-methyltetrahydrofolic acid in plasma. Based upon an isotope-dilution internal standard calibration study with standards, the LC–MS limit of quantitation for 5M-THF was estimated to be 0.39 ng/ml. 相似文献
143.
S.?N.?BurgessEmail author M.?T.?McCulloch G.?E.?Mortimer T.?M.?Ward 《Coral reefs (Online)》2009,28(4):1005-1015
The high-latitude coral species Plesiastrea versipora was investigated to identify growth rates in colonies over 1 m in diameter. Six colonies from two temperate gulfs (latitudes
of 33°–35°S) in Southern Australia were examined using X-ray, luminescence and 238U/230Th dating techniques. Annual density bands were present in each coral but varied in width and definition, suggesting different
linear extension and calcification rates. Differences in density band width were observed at the local scale (amongst colonies
on the same reef) and regional scales (between the two gulfs). Extension rates of the P. versipora colonies examined in this study varied between 1.2 and 7 mm per year, which are amongst the slowest growth rates reported
for hermatypic corals. As only one of the six P. versipora colonies had obvious luminescent banding, we conclude that luminescent banding is not an accurate chronological marker in
this species of temperate water coral. Coral age estimates derived from counting density bands in X-radiographs ranged from
90 to 320 years for the six colonies studied. U-Th ages from the same colonies determined by high-precision multi-collector
inductively coupled plasma mass spectrometer established radiometric ages between 105 and 381 years. The chronological variation
in absolute ages between the two techniques varied between 2 and 19% in different colonies, with the lowest growth rates (~1 mm)
displaying the greatest variation between density band age and radiometric U-Th age. This result implies that the age of P. versipora and other slow-growing corals cannot be determined accurately from density bands alone. The outcome of this research demonstrates
that P. versipora may be useful as a paleoclimate archive, recording several centuries in a single colony in high-latitude environments (corals
found in latitudes greater than 30° in either hemisphere), where other well-established coral climate archives, such as Porites, do not occur. 相似文献
144.
Foraging habits in a generalist predator: Sex and age influence habitat selection and resource use among bottlenose dolphins (Tursiops truncatus) 下载免费PDF全文
Sam Rossman Elizabeth Berens McCabe Hasand Gandhi Peggy H. Ostrom Craig A. Stricker Randall S. Wells 《Marine Mammal Science》2015,31(1):155-168
This study examines resource use (diet, habitat use, and trophic level) within and among demographic groups (males, females, and juveniles) of bottlenose dolphins (Tursiops truncatus). We analyzed the δ13C and δ15N values of 15 prey species constituting 84% of the species found in stomach contents. We used these data to establish a trophic enrichment factor (TEF) to inform dietary analysis using a Bayesian isotope mixing model. We document a TEF of 0‰ and 2.0‰ for δ13C and δ15N, respectively. The dietary results showed that all demographic groups relied heavily on low trophic level seagrass‐associated prey. Bayesian standard ellipse areas (SEAb) were calculated to assess diversity in resource use. The SEAb of females was nearly four times larger than that of males indicating varied resource use, likely a consequence of small home ranges and habitat specialization. Juveniles possessed an intermediate SEAb, generally feeding at a lower trophic level compared to females, potentially an effect of natal philopatry and immature foraging skills. The small SEAb of males reflects a high degree of specialization on seagrass associated prey. Patterns in resource use by the demographic groups are likely linked to differences in the relative importance of social and ecological factors. 相似文献
145.
Ibrahim GM Akiyama T Ochi A Otsubo H Smith ML Taylor MJ Donner E Rutka JT Snead OC Doesburg SM 《PloS one》2012,7(6):e39326
Although children with epilepsy exhibit numerous neurological and cognitive deficits, the mechanisms underlying these impairments remain unclear. Synchronization of oscillatory neural activity in the gamma frequency range (>30 Hz) is purported to be a mechanism mediating functional integration within neuronal networks supporting cognition, perception and action. Here, we tested the hypothesis that seizure-induced alterations in gamma synchronization are associated with functional deficits. By calculating synchrony among electrodes and performing graph theoretical analysis, we assessed functional connectivity and local network structure of the hand motor area of children with focal epilepsy from intracranial electroencephalographic recordings. A local decrease in inter-electrode phase synchrony in the gamma bands during ictal periods, relative to interictal periods, within the motor cortex was strongly associated with clinical motor weakness. Gamma-band ictal desychronization was a stronger predictor of deficits than the presence of the seizure-onset zone or lesion within the motor cortex. There was a positive correlation between the magnitude of ictal desychronization and impairment of motor dexterity in the contralateral, but not ipsilateral hand. There was no association between ictal desynchronization within the hand motor area and non-motor deficits. This study uniquely demonstrates that seizure-induced disturbances in cortical functional connectivity are associated with network-specific neurological deficits. 相似文献
146.
Saponins are glycosidic compounds present in many edible and inedible plants. They exhibit potent biological activities in mammalian systems, including several beneficial effects such as anti-inflammation and immunomodulation. In this study, we investigated the effects of seven platycodin saponins on the activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase II (COX-2) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. We found that 2"-O-acetyl polygalacin D (S1), platycodin A (S2), platycodin D (S3), and polygalacin D (S6) inhibited LPS-induced NO production in a concentration-dependent manner. Furthermore, these compounds inhibited the expression of LPS-induced iNOS and COX-2 protein and mRNA without an appreciable cytotoxic effect on RAW 264.7 macrophages, and could suppress induction by LPS of pro-inflammatory cytokines such as prostaglandin E2 (PGE2). Treatment with these compounds of RAW 264.7 cells transfected with a reporter construct indicated a reduced level of LPS-induced nuclear factor-kappaB (NF-kappaB) activity and effectively lowered NF-kappaB binding as measured by electrophoretic mobility shift assay (EMSA). The suppression of NF-kappaB activation appears to occur through the prevention of inhibitor kappaB (IkappaB) degradation. In vivo, platycodin saponin mixture (PS) and S3 protected mice from the lethal effects of LPS. The 89% lethality induced by LPS/galactosamine was reduced to 60% and 50% when PS and S3, respectively, were administered simultaneously with LPS. These results suggest that the main inhibitory mechanism of the platycodin saponins may be the reduction of iNOS and COX-2 gene expression through blocking of NF-kappaB activation. 相似文献
147.
The mechanism of the antitumor action of polyinosinic-polycytidylic acid is probably multifaceted. The compound induces the synthesis of interferon, and interferon probably is active against some tumors. Poly I:poly C alters protein and RNA synthesis in tissue culture. It specifically inhibits such macromolecule synthesis in tumors in vivo, while having less inhibitory action on synthesis in normal organs, or it may actually enhance. Finally, poly I:poly C strongly enhances graft vs. host rejection mechanisms, which may play a role in the rejection of some tumors. 相似文献
148.
Members of the yeast p24 family, including Emp24p and Erv25p, exist as heteromeric complexes that have been proposed to cycle between the endoplasmic reticulum (ER) and Golgi compartments. The specific functions and sites of action of p24 proteins are still unknown. Here we identified a human homolog of the yeast p24 family of proteins, named ERS25 (endoplasmic reticulum stress-response protein 25), and investigated its role in stress response. ERS25 is predicted to have an ER localization signal peptide, a GOLD (Golgi dynamics) domain, which is found in several eukaryotic Golgi and lipid-trafficking proteins, a coiled-coil region, and a transmembrane domain. We demonstrate that ERS25 is localized to the ER and is induced by ER-specific stress, heat shock, and oxidative stress. The selective induction of ERS25 by brefeldin A, but not tunicamycin, implicates the involvement of ERS25 in protein trafficking between the ER and the Golgi. Small interfering RNA-mediated inhibition of ERS25 results in a significant decrease in apoptosis as well as a reduction of reactive oxygen species induced by oxidative stress. Moreover, ERS25 depletion results in a significant increase in the levels of the ER chaperone HSP70 in response to heat-shock stress through increased levels of HSF-1. We also found that inhibition of ERS25 induction in response to heat shock enhanced the binding of HSP70 to Apaf-1, which is likely to interfere in stress-mediated apoptosis. Together, the data presented here demonstrate that ERS25 may play a critical role in regulation of heat-shock response and apoptosis. 相似文献
149.
Andrew A. Sproul Samson Jacob Deborah Pre Soong Ho Kim Michael W. Nestor Miriam Navarro-Sobrino Ismael Santa-Maria Matthew Zimmer Soline Aubry John W. Steele David J. Kahler Alex Dranovsky Ottavio Arancio John F. Crary Sam Gandy Scott A. Noggle 《PloS one》2014,9(1)
Presenilin 1 (PSEN1) encodes the catalytic subunit of γ-secretase, and PSEN1 mutations are the most common cause of early onset familial Alzheimer''s disease (FAD). In order to elucidate pathways downstream of PSEN1, we characterized neural progenitor cells (NPCs) derived from FAD mutant PSEN1 subjects. Thus, we generated induced pluripotent stem cells (iPSCs) from affected and unaffected individuals from two families carrying PSEN1 mutations. PSEN1 mutant fibroblasts, and NPCs produced greater ratios of Aβ42 to Aβ40 relative to their control counterparts, with the elevated ratio even more apparent in PSEN1 NPCs than in fibroblasts. Molecular profiling identified 14 genes differentially-regulated in PSEN1 NPCs relative to control NPCs. Five of these targets showed differential expression in late onset AD/Intermediate AD pathology brains. Therefore, in our PSEN1 iPSC model, we have reconstituted an essential feature in the molecular pathogenesis of FAD, increased generation of Aβ42/40, and have characterized novel expression changes. 相似文献
150.
Hui Liu Xiang Li Matthew D. Dun Sam Faulkner Chen Chen Jiang Hubert Hondermarck 《Proteomics》2020,20(10)
Pancreatic cancer has a dismal prognosis and to date there are no targeted therapies for this malignancy. Using shotgun proteomics, the mRNA binding protein cold shock domain containing E1 (CSDE1), also called upstream‐of‐N‐Ras, is detected in pancreatic cancer cell lines but not in normal pancreatic epithelial cells. The expression of CSDE1 in pancreatic cancer cells is confirmed by Western blotting and immunohistochemistry of human pancreatic tumors. In vitro functional assays show that siRNA downregulation of CSDE1 or gene knockout using CRISPR‐Cas9 significantly reduce the invasiveness of pancreatic cancer cells. Together, this study reveals that CSDE1 is overexpressed in pancreatic cancer and is a potential therapeutic target to inhibit pancreatic cancer cell invasion. 相似文献