全文获取类型
收费全文 | 142178篇 |
免费 | 22967篇 |
国内免费 | 6855篇 |
出版年
2024年 | 221篇 |
2023年 | 1493篇 |
2022年 | 3393篇 |
2021年 | 5976篇 |
2020年 | 5505篇 |
2019年 | 7761篇 |
2018年 | 7875篇 |
2017年 | 7106篇 |
2016年 | 8603篇 |
2015年 | 10693篇 |
2014年 | 11713篇 |
2013年 | 12638篇 |
2012年 | 12367篇 |
2011年 | 10948篇 |
2010年 | 8698篇 |
2009年 | 6770篇 |
2008年 | 6813篇 |
2007年 | 5730篇 |
2006年 | 5125篇 |
2005年 | 4028篇 |
2004年 | 3599篇 |
2003年 | 3137篇 |
2002年 | 2705篇 |
2001年 | 2355篇 |
2000年 | 2144篇 |
1999年 | 2040篇 |
1998年 | 1089篇 |
1997年 | 1190篇 |
1996年 | 1054篇 |
1995年 | 959篇 |
1994年 | 976篇 |
1993年 | 682篇 |
1992年 | 1031篇 |
1991年 | 863篇 |
1990年 | 640篇 |
1989年 | 583篇 |
1988年 | 513篇 |
1987年 | 426篇 |
1986年 | 407篇 |
1985年 | 403篇 |
1984年 | 224篇 |
1983年 | 210篇 |
1982年 | 148篇 |
1981年 | 127篇 |
1980年 | 115篇 |
1979年 | 122篇 |
1978年 | 85篇 |
1977年 | 65篇 |
1974年 | 79篇 |
1972年 | 70篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
71.
The molecular mechanism that controls the proliferation and differentiation of prostate epithelial cells is currently unknown. We previously identified a 44-kDa protein (p44/wdr77) as an androgen receptor-interacting protein that regulates a set of androgen receptor target genes in prostate epithelial cells and prostate cancer. In this study, we found that p44 localizes in the cytoplasm of prostate epithelial cells at the early stage of prostate development when cells are proliferating, and its nuclear translocation is associated with cellular and functional differentiation in adult prostate tissue. We further demonstrated that cytoplasmic p44 protein is essential for proliferation of prostate epithelial cells, whereas nuclear p44 is required for cell differentiation and prostate- specific protein secretion. These studies suggest a novel mechanism by which proliferation and differentiation of prostate epithelial cells are controlled by p44’s location in the cell. 相似文献
72.
N. Rocks C. Estrella G. Paulissen F. Quesada‐Calvo C. Gilles M. M. Guéders C. Crahay J.‐M. Foidart P. Gosset A. Noel D. D. Cataldo 《Cell proliferation》2008,41(6):988-1001
Abstract. Objectives: The ADAMs (a disintegrin and metalloproteinase) enzymes compose a family of membrane‐bound proteins characterized by their multi‐domain structure and ADAM‐12 expression is elevated in human non‐small cell lung cancers. The aim of this study was to investigate the roles played by ADAM‐12 in critical steps of bronchial cell transformation during carcinogenesis. Materials and methods: To assess the role of ADAM‐12 in tumorigenicity, BEAS‐2B cells were transfected with a plasmid encoding human full‐length ADAM‐12 cDNA, and then the effects of ADAM‐12 overexpression on cell behaviour were explored. Treatment of clones with heparin‐binding epidermal growth factor (EGF)‐like growth factor (HB‐EGF) neutralizing antibodies as well as an EGFR inhibitor allowed the dissection of mechanisms regulating cell proliferation and apoptosis. Results: Overexpression of ADAM‐12 in BEAS‐2B cells promoted cell proliferation. ADAM‐12 overexpressing clones produced higher quantities of HB‐EGF in their culture medium which may rely on membrane‐bound HB‐EGF shedding by ADAM‐12. Targeting HB‐EGF activity with a neutralizing antibody abrogated enhanced cell proliferation in the ADAM‐12 overexpressing clones. In sharp contrast, targeting of amphiregulin, EGF or transforming growth factor‐α failed to influence cell proliferation; moreover, ADAM‐12 transfectants were resistant to etoposide‐induced apoptosis and the use of a neutralizing antibody against HB‐EGF activity restored rates of apoptosis to be similar to controls.Conclusions: ADAM‐12 contributes to enhancing HB‐EGF shedding from plasma membranes leading to increased cell proliferation and reduced apoptosis in this bronchial epithelial cell line. 相似文献
73.
Improving farming practices of soil and water conservation has profound effects on the yield of wheat (Triticum aestivum L.) in dryland farming regions of the Loess Plateau in China. Mulching has proven to be an effective practice to increase crop yield, and possibly contribute to replenishing groundwater. This evaluation study collected and analyzed the data of 1849 observations published in 38 papers using meta-analysis to investigate effects of the mulching practices on wheat yield in terms of different rainfall and regions in comparison with conventional tillage. The main results of the study follow. The effects of the mulching practices were ranked in the order of RFM (ridge–furrow mulching) > MTMC (mulching with two materials combined) > MOM (mulching with other materials) > WSM (wheat straw mulching) > FM (flat mulching). The effects of the mulching practices at the different levels of rainfall during the wheat growing season were in the order: (< 150 mm) > (> 250 mm) > (150–250 mm). The effects of the mulching practices in the different regions were in the order of Henan > Shanxi > Shaanxi > Gansu. WSM, MTMC and FM performed better in improving wheat yield for rainfall of < 150, 150–250 and > 250 mm during the growing season, respectively. The wheat yield with FM, MTMC, MOM and MOM was higher than those with the other mulching practices in Shaanxi, Gansu, Henan and Shanxi. The wheat yield with RFM was 27.4% higher than that with FM, indicating that RFM was the most effective practice to improve wheat yield among all the practices. These findings have important implications for choosing appropriate crop field management to improve wheat yield. 相似文献
74.
During the process optimisation of glucoamylase production by Aspergillus awamori, cell morphology was controlled at such a state that spore aggregation was completely prevented. Samples from five fermentations on complex media using either glucose or starch as carbon source were characterised with a Bohlin CS rheometer. The experimental data were conveniently described in terms of the power law model. 相似文献
75.
Christopher A. Fraker Camillo Ricordi Luca Inverardi Juan Domínguez‐Bendala 《Biology of the cell / under the auspices of the European Cell Biology Organization》2009,101(8):431-440
Beyond its role as an electron acceptor in aerobic respiration, oxygen is also a key effector of many developmental events. The oxygen‐sensing machinery and the very fabric of cell identity and function have been shown to be deeply intertwined. Here we take a first look at how oxygen might lie at the crossroads of at least two of the major molecular pathways that shape pancreatic development. Based on recent evidence and a thorough review of the literature, we present a theoretical model whereby evolving oxygen tensions might choreograph to a large extent the sequence of molecular events resulting in the development of the organ. In particular, we propose that lower oxygenation prior to the expansion of the vasculature may favour HIF (hypoxia inducible factor)‐mediated activation of Notch and repression of Wnt/β‐catenin signalling, limiting endocrine cell differentiation. With the development of vasculature and improved oxygen delivery to the developing organ, HIF‐mediated support for Notch signalling may decline while the β‐catenin‐directed Wnt signalling is favoured, which would support endocrine cell differentiation and perhaps exocrine cell proliferation/differentiation. 相似文献
76.
77.
Kendra I. Siler‐Marsiglio Gerry Shaw Marieta B. Heaton 《Developmental neurobiology》2004,59(3):261-271
Pycnogenol® (PYC), a patented combination of bioflavonoids extracted from the bark of French maritime pine (Pinus maritima), scavenges free radicals and promotes cellular health. The protective capacity of PYC against ethanol toxicity of neurons has not previously been explored. The present study demonstrates that in postnatal day 9 (P9) rat cerebellar granule cells the antioxidants vitamin E (VE) and PYC (1) dose dependently block cell death following 400, 800, and 1600 mg/dL ethanol exposure (2) inhibit the ethanol‐induced activation of caspase‐3 in the same model system; and (3) reduce neuronal membrane disruption as assayed by phosphatidylserine translocation to the cell surface. These results suggest that both PYC and VE have the potential to act as therapeutic agents, antagonizing the induction of neuronal cell death by ethanol exposure. © 2004 Wiley Periodicals, Inc. J Neurobiol 59: 261–271, 2004 相似文献
78.
Nacrein-like proteins have carbonic anhydrase (CA)-like domains, but their coding regions are flanked by inserted repeat sequence, such as Gly-X-Asn. Reportedly, nacrein-like proteins show the highest similarity to human carbonic anhydrase 1(α-CA1), possess CA catalytic functions, and play a key role in shell biomineralization. In the present study, two novel nacrein-like proteins were firstly identified from the shell-forming mantle of the Pacific oyster Crassostrea gigas. With numerous analyses, it was identified and characterized that both the nacrein-like proteins F1 and F2 were secreted and most closely related to the nacrein-like protein of California mussel Mytilus californianus via phylogenetic analysis. RT-PCR analysis showed that the nacrein-like proteins F1 and F2 were expressed in multiple tissues and the expression levels remarkably rose after entering the spat stage, which were basically consistent with the increase of calcite fractions in the total shell volume. Surprisingly, the Gly-X-Asn repeat domain, which is distinctive in most nacrein-like proteins, was absent in the two newly identified nacrein-like proteins in C. gigas and replaced with a series of acidic amino acids (D/E). Regardless, nacrein-like proteins in mollusks seem to be vital to the deposition of calcium carbonate and likely perform diverse functions. 相似文献
79.
1. Worldwide, the excessive use of insecticides has resulted in field-evolved insecticide-resistant populations of diamondback moth (DBM), Plutella xylostella. A deltamethrin-resistant DBM population from the field was divided into two subpopulations in the laboratory. One population (S-strain) was maintained with no further exposure to insecticides, whereas the other population (R-strain) was maintained under a regime of intermittent selection with deltamethrin. 2. Individuals from both strains were reared at constant temperatures in the range 10–35 °C in the absence of deltamethrin, and the effects of rearing temperature on various traits were investigated. At the time of experimentation, the R-strain was 20-fold more resistant to deltamethrin than the S-strain. 3. Temperature differentially affected developmental time, adult life span, pupal weight, and fecundity of both strains. Although both strains laid eggs after being reared at 10 °C, few of these eggs were fertile. The R-strain developed significantly faster than the S-strain. The integrated performance of the S-strain and R-strain was greatest at 25 and 15 °C, respectively. 4. The present study provides important information on the complexities of the outcomes of the interactions between ectotherms and temperature. Specifically, temperature-trait relationships may not be unimodal, and ectotherm genotypes (in this case insecticide-resistance status) and abiotic stresses can interact with unpredictable outcomes. 5. Current models predicting DBM population dynamics and relative abundance in different locations do not consider different thermal biologies of different genotypes. The present study shows the dramatic effects of environment on many parameters used in these models and will help to enhance their accuracy, and thus their utility. 相似文献
80.