全文获取类型
收费全文 | 12135篇 |
免费 | 1003篇 |
国内免费 | 438篇 |
专业分类
13576篇 |
出版年
2024年 | 35篇 |
2023年 | 278篇 |
2022年 | 350篇 |
2021年 | 493篇 |
2020年 | 477篇 |
2019年 | 661篇 |
2018年 | 584篇 |
2017年 | 447篇 |
2016年 | 465篇 |
2015年 | 443篇 |
2014年 | 930篇 |
2013年 | 1210篇 |
2012年 | 679篇 |
2011年 | 793篇 |
2010年 | 611篇 |
2009年 | 553篇 |
2008年 | 629篇 |
2007年 | 610篇 |
2006年 | 439篇 |
2005年 | 376篇 |
2004年 | 300篇 |
2003年 | 205篇 |
2002年 | 161篇 |
2001年 | 114篇 |
2000年 | 99篇 |
1999年 | 99篇 |
1998年 | 125篇 |
1997年 | 79篇 |
1996年 | 69篇 |
1995年 | 73篇 |
1994年 | 60篇 |
1993年 | 56篇 |
1992年 | 60篇 |
1991年 | 49篇 |
1990年 | 39篇 |
1989年 | 33篇 |
1988年 | 42篇 |
1985年 | 129篇 |
1984年 | 119篇 |
1983年 | 73篇 |
1982年 | 86篇 |
1981年 | 72篇 |
1980年 | 71篇 |
1979年 | 55篇 |
1978年 | 46篇 |
1977年 | 41篇 |
1976年 | 26篇 |
1975年 | 23篇 |
1974年 | 36篇 |
1973年 | 24篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
71.
Richard J. Smith 《American journal of physical anthropology》2019,169(4):591-598
The establishment of cause and effect relationships is a fundamental objective of scientific research. Many lines of evidence can be used to make cause–effect inferences. When statistical data are involved, alternative explanations for the statistical relationship need to be ruled out. These include chance (apparent patterns due to random factors), confounding effects (a relationship between two variables because they are each associated with an unmeasured third variable), and sampling bias (effects due to preexisting properties of compared groups). The gold standard for managing these issues is a controlled randomized experiment. In disciplines such as biological anthropology, where controlled experiments are not possible for many research questions, causal inferences are made from observational data. Methods that statisticians recommend for this difficult objective have not been widely adopted in the biological anthropology literature. Issues involved in using statistics to make valid causal inferences from observational data are discussed. 相似文献
72.
Lina Assad Melvin M. Schwartz Ismo Virtanen Victor E. Gould 《Virchows Archiv. B, Cell pathology including molecular pathology》1993,63(1):307-316
Frozen samples of minimal change glomerulopathy (MCG), and of membranous, segmental and diffuse lupus glomerulonephritis (MGN,
SGN, DLGN) were studied to assess the distribution of tenascin (Ten), and the extradomains A and B (EDA-and EDB-) and oncofetal
(Onc-) isoforms of cellular fibronectin (cFn). Cryosections were immunostained by the ABC method with specific monoclonal
antibodies. In MCG, mesangial Ten and EDA-cFn reactions were increased. In MGN, mesangial Ten and EDA-cFn staining was enhanced
except in segmental scars; convincing reactions were seen in cases with membranous transformation; spikes stained strongly.
In SGN, variably intense staining for Ten and all cFn isoforms was seen in glomerular necrosis, proliferation and crescents;
parietal epithelium EDA-cFn staining was noted. In DLGN, strong and extensive mesangial Ten and EDA-cFn staining was seen
as were focal EDB-and Onc-cFn reactions. Parietal cells with and without crescents stained variably with all Mabs. Obsolete
glomeruli were unreactive save for rare periglomerular Ten rims. Interstitial inflammation and fibrosis in MGN, SGN and DLGN
had moderate to strong Ten and EDA-cFn staining with rare traces of EDB-and Onc-cFn. We conclude that enhanced Ten and EDA-cFn
is a potentially reversible response to glomerular injury whereas the expression of EDB-and Onc-cFn apparently result from
necrosis and/or cellular proliferation which lead to scarring. And, while mesangial cells are the major source of these molecules,
epithelial cells might also partake in their synthesis. 相似文献
73.
Silurian calcispheres (Calcitarcha) of Gotland (Sweden): Comparisons with calcareous dinoflagellates
Scanning electron microscope examinations of polished and etched surfaces of sediments from the Silurian carbonate platform of Gotland, Sweden, revealed the presence of numerous, morphologically diverse “calcispheres” (Calcitarcha). Some of these spherical calcareous microfossils display wall structures that are surprisingly similar to those of calcareous dinoflagellate cysts. In analogy to the interpretation of the biological affinities of Palaeozoic acritarchs as cysts of organisms that might have been the ancestors of organic-walled dinoflagellates, the Calcitarcha from Gotland can be compared and may possibly be related to organisms that may have been the ancestors of calcareous cyst-producing dinoflagellates that so far have not been observed before the Late Jurassic. 相似文献
74.
Generalized estimating equations (GEE) are extension of generalized linear models (GLM) widely applied in longitudinal data analysis. GEE are also applied in spatial data analysis using geostatistics methods. In this paper, we advocate application of GEE for spatial lattice data by modeling the spatial working correlation matrix using the Moran's index and the spatial weight matrix. We present theoretical developments and results for simulated and actual data as well. For the former case, 1,000 samples of a random variable (response variable) defined in (0, 1) interval were generated using different values of the Moran's index. In addition, 1,000 samples of a binary and a continuous variable were also randomly generated as covariates. In each sample, three structures of spatial working correlation matrices were used while modeling: The independent, autoregressive, and the Toeplitz structure. Two measures were used to evaluate the performance of each of the spatial working correlation structures: the asymptotic relative efficiency and the working correlation selection criterions. The results showed that both measures indicated that the autoregressive spatial working correlation matrix proposed in this paper presents the best performance in general. For the actual data case, the proportion of small farmers who used improved maize varieties was considered as the response variable and a set of nine variables were used as covariates. Two structures of spatial working correlation matrices were used and the results showed consistence with those obtained in the simulation study. 相似文献
75.
Sophie Calderari Massimiliano Ria Christelle Gérard Tatiane C. Nogueira Olatz Villate Stephan C. Collins Helen Neil Nicolas Gervasi Christophe Hue Nicolas Suarez-Zamorano Cécilia Prado Miriam Cnop Marie-Thérèse Bihoreau Pamela J. Kaisaki Jean-Baptiste Cazier Cécile Julier Mark Lathrop Michel Werner Dominique Gauguier 《Genomics》2018,110(2):98-111
The GLIS family zinc finger 3 isoform (GLIS3) is a risk gene for Type 1 and Type 2 diabetes, glaucoma and Alzheimer's disease endophenotype. We identified GLIS3 binding sites in insulin secreting cells (INS1) (FDR q < 0.05; enrichment range 1.40–9.11 fold) sharing the motif wrGTTCCCArTAGs, which were enriched in genes involved in neuronal function and autophagy and in risk genes for metabolic and neuro-behavioural diseases. We confirmed experimentally Glis3-mediated regulation of the expression of genes involved in autophagy and neuron function in INS1 and neuronal PC12 cells. Naturally-occurring coding polymorphisms in Glis3 in the Goto-Kakizaki rat model of type 2 diabetes were associated with increased insulin production in vitro and in vivo, suggestive alteration of autophagy in PC12 and INS1 and abnormal neurogenesis in hippocampus neurons. Our results support biological pleiotropy of GLIS3 in pathologies affecting β-cells and neurons and underline the existence of trans?nosology pathways in diabetes and its co-morbidities. 相似文献
76.
Spatial and temporal phenotypic differentiation in mean body size is of commonplace occurrence, but the underlying causes remain often unclear: both genetic differentiation in response to selection (or drift) and environmentally induced plasticity can create similar phenotypic patterns. Studying changes in body mass in Siberian jays (Perisoreus infaustus) over three decades, we discovered that mean body mass declined drastically (ca. 10%) over the first two decades, but increased markedly thereafter back to almost the initial level. Quantitative genetic analyses revealed that although body mass was heritable (h2 = 0.46), the pronounced temporal decrease in body mass was mainly a product of phenotypic plasticity. However, a concomitant and statistically significant decrease in predicted breeding values suggests a genetic component to this change. The subsequent increase in mean body mass was indicated to be entirely due to plasticity. Selection on body mass was estimated to be too weak to fully account for the observed genetic decline in body mass, but bias in selection differential estimates due to environmental covariance between body mass and fitness is possible. Hence, the observed body mass changes appear to be driven mainly by phenotypic plasticity. Although we were not able to identify the ecological driver of the observed plastic changes, the results highlight the utility of quantitative genetic approaches in disentangling genetic and phenotypic changes in natural populations. 相似文献
77.
78.
Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits 下载免费PDF全文
Clara Ortega‐de San Luis Manuel A. Sanchez‐Garcia Jose Luis Nieto‐Gonzalez Pablo García‐Junco‐Clemente Adoracion Montero‐Sanchez Rafael Fernandez‐Chacon Alberto Pascual 《Aging cell》2018,17(5)
The striatum integrates motor behavior using a well‐defined microcircuit whose individual components are independently affected in several neurological diseases. The glial cell line‐derived neurotrophic factor (GDNF), synthesized by striatal interneurons, and Sonic hedgehog (Shh), produced by the dopaminergic neurons of the substantia nigra (DA SNpc), are both involved in the nigrostriatal maintenance but the reciprocal neurotrophic relationships among these neurons are only partially understood. To define the postnatal neurotrophic connections among fast‐spiking GABAergic interneurons (FS), cholinergic interneurons (ACh), and DA SNpc, we used a genetically induced mouse model of postnatal DA SNpc neurodegeneration and separately eliminated Smoothened (Smo), the obligatory transducer of Shh signaling, in striatal interneurons. We show that FS postnatal survival relies on DA SNpc and is independent of Shh signaling. On the contrary, Shh signaling but not dopaminergic striatal innervation is required to maintain ACh in the postnatal striatum. ACh are required for DA SNpc survival in a GDNF‐independent manner. These data demonstrate the existence of three parallel but interdependent neurotrophic relationships between SN and striatal interneurons, partially defined by Shh and GDNF. The definition of these new neurotrophic interactions opens the search for new molecules involved in the striatal modulatory circuit maintenance with potential therapeutic value. 相似文献
79.
Pseudomonas aeruginosa (P. aeruginosa) is a highly pathogenic bacteria involved in numerous diseases among which, are urinary tract infections (UTIs). The pyocyanin secreted as a virulence factor by this bacterium has many beneficial applications but its high cost remains an obstacle for its widespread use. In this study, a total of fifty urine isolates were identified as P. aeruginosa. All strains produced pyocyanin pigment with a range of 1.3–31 µg/ml. The highest producer clinical strain P21 and the standard strain PA14 were used in optimization of pyocyanin production. Among tested media, king’s A fluid medium resulted in the highest yield of pyocyanin pigment followed by nutrient broth. Growth at 37 °C was superior in pyocyanin production than growth at 30 °C. Both shaking and longer incubation periods (3–4 days) improved pyocyanin production. The pyocyanin yield was indifferent upon growth of P21 at both pH 7 and pH 8. In conclusion, the optimum conditions for pyocyanin production are to use King’s A fluid medium of pH 7 and incubate the inoculated medium at 37 °C with shaking at 200 rpm for a period of three to four days. 相似文献
80.
Xiao Zhang Xixin He Qiuhe Chen Junfeng Lu Simona Rapposelli Rongbiao Pi 《Bioorganic & medicinal chemistry》2018,26(3):543-550
Alzheimer’s disease (AD), a complex chronic progressive central nervous system degenerative disease and a public health problem of the world, often characters cognitive dysfunction accompaning aggression and depression, and may lead to death. More attentions should be paid on it because there is no modified strategy against AD till now. AD is featured with the loss of cholinergic neurons, the amyloid-beta peptide (Aβ) plaques and the neurofibrillary tangles and several hypotheses were established to explain the pathogenesis of AD. Hydroxycinnamic acids, including caffeic acid (CA) and ferulic acid (FA) are widely distributed in natural plants and fruits. CA and FA exert various pharmacological activities, including anti-inflammatory, antioxidant, neuroprotection, anti-amyloid aggregation and so on. All these pharmacological activities are associated with the treatment of AD. Here we summarized the pharmacological activities of CA and FA, and their hybrids as multi-target-directed ligands (MTDLs) against AD. The future application of CA and FA was also discussed, hoping to provide beneficial information for the development of CA- and FA-based MTDLs against AD. 相似文献