全文获取类型
收费全文 | 120436篇 |
免费 | 2379篇 |
国内免费 | 2433篇 |
专业分类
125248篇 |
出版年
2024年 | 64篇 |
2023年 | 345篇 |
2022年 | 831篇 |
2021年 | 1405篇 |
2020年 | 961篇 |
2019年 | 1189篇 |
2018年 | 12696篇 |
2017年 | 11231篇 |
2016年 | 8475篇 |
2015年 | 2459篇 |
2014年 | 2396篇 |
2013年 | 2562篇 |
2012年 | 6716篇 |
2011年 | 14837篇 |
2010年 | 13240篇 |
2009年 | 9326篇 |
2008年 | 11159篇 |
2007年 | 12554篇 |
2006年 | 1410篇 |
2005年 | 1469篇 |
2004年 | 1739篇 |
2003年 | 1698篇 |
2002年 | 1301篇 |
2001年 | 732篇 |
2000年 | 537篇 |
1999年 | 434篇 |
1998年 | 250篇 |
1997年 | 286篇 |
1996年 | 261篇 |
1995年 | 214篇 |
1994年 | 223篇 |
1993年 | 179篇 |
1992年 | 236篇 |
1991年 | 221篇 |
1990年 | 137篇 |
1989年 | 113篇 |
1988年 | 96篇 |
1987年 | 121篇 |
1986年 | 82篇 |
1985年 | 69篇 |
1984年 | 59篇 |
1983年 | 53篇 |
1982年 | 38篇 |
1981年 | 26篇 |
1979年 | 25篇 |
1975年 | 26篇 |
1972年 | 263篇 |
1971年 | 285篇 |
1965年 | 22篇 |
1962年 | 26篇 |
排序方式: 共有10000条查询结果,搜索用时 10 毫秒
941.
Intracellular Ca2+ is vital for cell physiology. Disruption of Ca2+ homeostasis contributes to human diseases such as heart failure, neuron-degeneration, and diabetes. To ensure an effective
intracellular Ca2+ dynamics, various Ca2+ transport proteins localized in different cellular regions have to work in coordination. The central role of mitochondrial
Ca2+ transport mechanisms in responding to physiological Ca2+ pulses in cytosol is to take up Ca2+ for regulating energy production and shaping the amplitude and duration of Ca2+ transients in various micro-domains. Since the discovery that isolated mitochondria can take up large quantities of Ca2+ approximately 5 decades ago, extensive studies have been focused on the functional characterization and implication of ion
channels that dictate Ca2+ transport across the inner mitochondrial membrane. The mitochondrial Ca2+ uptake sensitive to non-specific inhibitors ruthenium red and Ru360 has long been considered as the activity of mitochondrial
Ca2+ uniporter (MCU). The general consensus is that MCU is dominantly or exclusively responsible for the mitochondrial Ca2+ influx. Since multiple Ca2+ influx mechanisms (e.g. L-, T-, and N-type Ca2+ channel) have their unique functions in the plasma membrane, it is plausible that mitochondrial inner membrane has more than
just MCU to decode complex intracellular Ca2+ signaling in various cell types. During the last decade, four molecular identities related to mitochondrial Ca2+ influx mechanisms have been identified. These are mitochondrial ryanodine receptor, mitochondrial uncoupling proteins, LETM1
(Ca2+/H+ exchanger), and MCU and its Ca2+ sensing regulatory subunit MICU1. Here, we briefly review recent progress in these and other reported mitochondrial Ca2+ influx pathways and their differences in kinetics, Ca2+ dependence, and pharmacological characteristics. Their potential physiological and pathological implications are also discussed. 相似文献
942.
A white rot fungus Phlebia tremellosa produced lignin degrading enzymes, which showed degrading activity against various recalcitrant compounds. However, manganese
peroxidase (MnP) activity, one of lignin degrading enzymes, was very low in this fungus under various culture conditions.
An expression vector that carried both the laccase and MnP genes was constructed using laccase genomic DNA of P. tremellosa and MnP cDNA from Polyporus brumalis. P. tremellosa was genetically transformed using the expression vector to obtain fungal transformants showing increased laccase and MnP
activity. Many transformants showed highly increased laccase and MnP activity at the same time in liquid medium, and three
of them were used to degrade endocrine disrupting chemicals. The transformant not only degraded bisphenol A and nonylphenol
more rapidly but also removed the estrogenic activities of the chemicals faster than the wild type strain. 相似文献
943.
944.
Diana Stralberg D. Richard Cameron Mark D. Reynolds Catherine M. Hickey Kirk Klausmeyer Sylvia M. Busby Lynne E. Stenzel W. David Shuford Gary W. Page 《Biodiversity and Conservation》2011,20(1):19-40
Conservation of migratory shorebirds and waterfowl presents unique challenges due to extensive historic loss of wetland habitats, and current reliance on managed landscapes for wintering and migratory passage. We developed a spatially-explicit approach to estimate potential shorebird and waterfowl densities in California by integrating mapped habitat layers and statewide bird survey data with expert-based habitat rankings. Using these density estimates as inputs, we used the Marxan site-selection program to identify priority shorebird and waterfowl areas at the ecoregional level. We identified 3.7 million ha of habitat for shorebirds and waterfowl, of which 1.4 million ha would be required to conserve 50% of wintering populations. To achieve a conservation goal of 75%, more than twice as much habitat (3.1 million ha) would be necessary. Agricultural habitats comprised a substantial portion of priority areas, especially at the 75% level, suggesting that under current management conditions, large areas of agricultural land, much of it formerly wetland, are needed to provide the habitat availability and landscape connectivity required by shorebird and waterfowl populations. These habitats were found to be largely lacking recognized conservation status in California (96% un-conserved), with only slightly higher levels of conservation for priority shorebird and waterfowl areas. Freshwater habitats, including wetlands and ponds, were also found to have low levels of conservation (67% un-conserved), although priority shorebird and waterfowl areas had somewhat higher levels of conservation than the state as a whole. Conserving migratory waterfowl and shorebirds will require a diversity of conservation strategies executed at a variety of scales. Our modeled results are complementary with other approaches and can help prioritize areas for protection, restoration and other actions. Traditional habitat protection strategies such as conservation easements and fee acquisitions may be of limited utility for protecting and managing significant areas of agricultural lands. Instead, conservation strategies focused on incentive-based programs to support wildlife friendly management practices in agricultural settings may have greater utility and conservation effectiveness. 相似文献
945.
946.
Aloke K. Bera Nancy W. Y. Ho Aftab Khan Miroslav Sedlak 《Journal of industrial microbiology & biotechnology》2011,38(5):617-626
Robust microorganisms are necessary for economical bioethanol production. However, such organisms must be able to effectively
ferment both hexose and pentose sugars present in lignocellulosic hydrolysate to ethanol. Wild type Saccharomyces cerevisiae can rapidly ferment hexose, but cannot ferment pentose sugars. Considerable efforts were made to genetically engineer S. cerevisiae to ferment xylose. Our genetically engineered S cerevisiae yeast, 424A(LNH-ST), expresses NADPH/NADH xylose reductase (XR) that prefer NADPH and NAD+-dependent xylitol dehydrogenase (XD) from Pichia stipitis, and overexpresses endogenous xylulokinase (XK). This strain is able to ferment glucose and xylose, as well as other hexose
sugars, to ethanol. However, the preference for different cofactors by XR and XD might lead to redox imbalance, xylitol excretion,
and thus might reduce ethanol yield and productivity. In the present study, genes responsible for the conversion of xylose
to xylulose with different cofactor specificity (1) XR from N. crassa (NADPH-dependent) and C. parapsilosis (NADH-dependent), and (2) mutant XD from P. stipitis (containing three mutations D207A/I208R/F209S) were overexpressed in wild type yeast. To increase the NADPH pool, the fungal
GAPDH enzyme from Kluyveromyces lactis was overexpressed in the 424A(LNH-ST) strain. Four pentose phosphate pathway (PPP) genes, TKL1, TAL1, RKI1 and RPE1 from S. cerevisiae, were also overexpressed in 424A(LNH-ST). Overexpression of GAPDH lowered xylitol production by more than 40%. However, other
strains carrying different combinations of XR and XD, as well as new strains containing the overexpressed PPP genes, did not
yield any significant improvement in xylose fermentation. 相似文献
947.
Ding Haixia Zhang Jingsong Jiang Lei Dong Hairong Wang Jun Xiao Hang Chen Weixian 《Cell biochemistry and biophysics》2011,59(1):39-47
Extracellular domains of the transmembrane glycoprotein, neuropilin-1 (Np1), specifically bind an array of factors and co-receptors
including class-3 semaphorins (Sema3a), vascular endothelial growth factor (VEGF), hepatocyte growth factor, platelet-derived
growth factor BB, transforming growth factor-β 1 (TGF-β1), and fibroblast growth factor2 (FGF2). Np1 may have a role in immune
response, tumor cell growth, and angiogenesis, but its relative expression in comparison to its co-primary receptors, VEGF
and Sema3a, is not known. In this study we determined the mRNA expression of Np1 and its co-receptors, VEGF and Sema3a, and
the ratio of VEGF/Sema3a in different human and rodent cell lines. Expression of Np1, VEGF and Sema3a is very low in cells
derived from normal tissues, but these proteins are highly expressed in tumor-derived cells. Furthermore, the ratio of VEGF/Sema3a
is highly variable in different tumor cells. The elevated mRNA expression of Np1 and its putative receptors in tumor cells
suggests a role for these proteins in tumor cell migration and angiogenesis. As different tumor cells exhibit varying VEGF/Sema3a
ratios, it appears that cancer cells show differential response to angiogenic factors. These results bring to light the individual
variation among the cancer-related genes, Np1, VEGF, and Sema3a, and provide an important impetus for the possible personalized
therapeutic approaches for cancer patients. 相似文献
948.
Mai Kanke Kohei Nishimura Masato Kanemaki Tatsuo Kakimoto Tatsuro S Takahashi Takuro Nakagawa Hisao Masukata 《BMC cell biology》2011,12(1):8
Background
Inducible inactivation of a protein is a powerful approach for analysis of its function within cells. Fission yeast is a useful model for studying the fundamental mechanisms such as chromosome maintenance and cell cycle. However, previously published strategies for protein-depletion are successful only for some proteins in some specific conditions and still do not achieve efficient depletion to cause acute phenotypes such as immediate cell cycle arrest. The aim of this work was to construct a useful and powerful protein-depletion system in Shizosaccaromyces pombe. 相似文献949.
950.
High salinity is an environmental factor that inhibits plant growth and development, leading to large losses in crop yields.
We report here that mutations in SIZ1 or PHO2, which cause more accumulation of phosphate compared with the wild type, enhance tolerance to salt stress. The siz1 and pho2 mutations reduce the uptake and accumulation of Na+. These mutations are also able to suppress the Na+ hypersensitivity of the sos3-1 mutant, and genetic analyses suggest that SIZ1 and SOS3 or PHO2 and SOS3 have an additive effect on the response to salt stress. Furthermore, the siz1 mutation cannot suppress the Li+ hypersensitivity of the sos3-1 mutant. These results indicate that the phosphate-accumulating mutants siz1 and pho2 reduce the uptake and accumulation of Na+, leading to enhanced salt tolerance, and that, genetically, SIZ1 and PHO2 are likely independent of SOS3-dependent salt signaling. 相似文献