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1.
It was found that S-adenosylmethionine (SAM) could effectively improve avermectin titer with 30–60 μg/mL addition to FH medium. To clearly elucidate the mechanism of SAM on intracellular metabolites of Streptomyces avermitilis, a GC–MS-based comparative metabolomics approach was carried out. First, 230 intracellular metabolites were identified and 14 of them remarkably influenced avermectin biosynthesis were discriminative biomarkers between non-SAM groups and SAM-treated groups by principal components analysis (PCA) and partial least squares (PLS). Based on further key metabolic pathway analyses, these biomarkers, such as glucose, oxaloacetic acid, fatty acids (in soybean oil), threonine, valine, and leucine, were identified as potentially beneficial precursors and added in medium. Compared with single-precursor feeding, the combined feeding of the precursors and SAM markedly increased the avermectin titer. The co-feeding approach not only directly verified our hypothesis on the mechanism of SAM by comparative metabolomics, but also provided a novel strategy to increase avermectin production.  相似文献   
2.
Chronic hepatitis is a major cause of liver cancer, so earlier treatment of hepatitis might be reducing liver cancer incidence. Hepatitis can be induced in mice by treatment with Concanavalin A (Con A); the resulting liver injury causes significant CD4+ T cell activation and infiltration. In these T cells, Roquin, a ring-type E3 ubiquitin ligase, is activated. To investigate the role of Roquin, we examined Con A-induced liver injury and T cell infiltration in transgenic (Tg) mice overexpressing Roquin specifically in T cells. In Roquin Tg mice, Con A treatment caused greater increases in both the levels of liver injury enzymes and liver tissue apoptosis, as revealed by TUNEL and H&E staining, than wild type (WT) mice. Further, Roquin Tg mice respond to Con A treatment with greater increases in the T cell population, particularly Th17 cells, though Treg cell counts are lower. Roquin overexpression also enhances increases in pro-inflammatory cytokines, including IFN-γ, TNF-α and IL-6, upon liver injury. Furthermore, Roquin regulates the immune response and apoptosis in Con A induced hepatitis via STATs, Bax and Bcl2. These findings suggest that over-expression of Roquin exacerbates T-cell mediated hepatitis.  相似文献   
3.
Cholesterosis is a disease of cholesterol metabolism characterized by the presence of excessive lipid droplets in the cytoplasm. These lipid droplets are mainly composed of cholesterol esters derived from free cholesterol. The removal of excess cholesterol from gallbladder epithelial cells (GBECs) is very important for the maintenance of intracellular cholesterol homeostasis and the preservation of gallbladder function. Several lines of evidence have indicated that the activation of either peroxisome proliferator-activated receptor gamma (PPARγ) or liver X receptor α (LXRα) relates to cholesterol efflux. While pioglitazone can regulate the activation of PPARγ, 22(R)-hydroxycholesterol can activate LXRα and is a metabolic intermediate in the biosynthesis of steroid hormones. However, the effect of 22(R)-hydroxycholesterol in combination with pioglitazone on cholesterosis of the gallbladder is unclear. GBECs were treated with pioglitazone, 22(R)-hydroxycholesterol or PPARγ siRNA followed by Western blot analysis for ATP-binding cassette transporter A1 (ABCA1), PPARγ and LXRα. Cholesterol efflux to apoA-I was determined, and Oil Red O staining was performed to monitor variations in lipid levels in treated GBECs. Our data showed that 22(R)-hydroxycholesterol can modestly up-regulate LXRα while simultaneously increasing ABCA1 by 56%. The combination of 22(R)-hydroxycholesterol and pioglitazone resulted in a 3.64-fold increase in ABCA1 expression and a high rate of cholesterol efflux. Oil Red O staining showed an obvious reduction in the lipid droplets associated with cholesterosis in GBECs. In conclusion, the present findings indicate that the anti-lipid deposition action of 22(R)-hydroxycholesterol combined with pioglitazone involves the activation of the PPARγ–LXRα–ABCA1 pathway, increased ABCA1 expression and the efflux of cholesterol from GBECs. Thus, 22(R)-hydroxycholesterol synergistically combined with pioglitazone to produce a remarkable effect on lipid deposition in cholesterosis GBECs.  相似文献   
4.
Peach Prunus persica (L.) Batsch is self-compatible and largely self-fertile, but under greenhouse conditions pollinators must be introduced to achieve good fruit set and quality. Because little work has been done to assess the effectiveness of different pollinators on peach trees under greenhouse conditions, we studied ‘Okubo’ peach in greenhouse tunnels near Beijing between 2012 and 2014. We measured pollen deposition, pollen-tube growth rates, ovary development, and initial fruit set after the flowers were visited by either of two managed pollinators: bumblebees, Bombus patagiatus Nylander, and honeybees, Apis mellifera L. The results show that B. patagiatus is more effective than A. mellifera as a pollinator of peach in greenhouses because of differences in two processes. First, B. patagiatus deposits more pollen grains on peach stigmas than A. mellifera, both during a single visit and during a whole day of open pollination. Second, there are differences in the fertilization performance of the pollen deposited. Half of the flowers visited by B. patagiatus are fertilized 9–11 days after bee visits, while for flowers visited by A. mellifera, half are fertilized 13–15 days after bee visits. Consequently, fruit development is also accelerated by bumblebees, showing that the different pollinators have not only different pollination efficiency, but also influence the subsequent time course of fertilization and fruit set. Flowers visited by B. patagiatus show faster ovary growth and ultimately these flowers produce more fruit. Our work shows that pollinators may influence fruit production beyond the amount of pollen delivered. We show that managed indigenous bumblebees significantly outperform introduced honeybees in increasing peach initial fruit set under greenhouse conditions.  相似文献   
5.
Cardiac atlases play an important role in the computer-aided diagnosis of cardiovascular diseases, in particular they need to deal with large and highly variable image datasets. In this paper, we propose a new nonrigid registration algorithm incorporating shape information, to produce comprehensive atlases. For one thing, the multiscale gradient orientation features of images are combined to form the construction of multifeature mutual information. Additionally, the shape information of multiple-objects in images is incorporated into the cost function for registration. We demonstrate the merits of the new registration algorithm on the 3D data sets of 15 patients. The experimental results show that the new registration algorithm can outperform the conventional intensity-based registration method. The obtained atlas can represent the cardiac structures more accurately.  相似文献   
6.
MethodsWe used Western blotting and immunohistochemistry to examine BIRC6 expression in 7 CRC cell lines and 126 CRC clinical samples. We determined the biological significance of BIRC6 in CRC cell lines by a lentivirus-mediated silencing method.ResultsWe reported that BIRC6 was overexpressed in CRC cell lines and clinical CRC tissues. BIRC6 overexpression was correlated with tumor size and invasion depth of CRC. BIRC6 overexpression is associated with worse overall survival (OS) (P = 0.001) and shorter disease-free survival (DFS) (P = 0.010). BIRC6 knockdown inhibited cell proliferation, arrested cell cycle at S phase, downregulated cyclin A2, B1, D1 and E1 levels, and sensitized CRC cells to chemotherapy in vitro and in vivo.ConclusionsTaken together, these data suggests that BIRC6 overexpression is a predictor of poor prognosis in colorectal cancer and BIRC6 could be a potential target of CRC therapy.  相似文献   
7.

Background

The present study was designed to determine whether the Thinprep plus Papanicolaou stain (Thinprep) method is more sensitive than the Cytospin-coupled Wright-Giemsa (WG) stain (Cytospin) method in diagnosis of leptomeningeal metastasis (LM) from malignant solid tumors in cerebrospinal fluid (CSF). We also explored if the Thinprep method could be used in the differential diagnosis of the type of primary tumor cells based on the morphology of tumor cells in CSF samples.

Methods

The morphological features of tumor cells in fresh CSF samples were analyzed using both methods. The tumor cell detection rates were compared between the two methods.

Results

Using the Thinprep method, we found that each type of tumor cells in the CSF samples had specific identifiable morphological features linked to their primary cancer origins, such as adenocarcinomas originated from the lungs, breast, and stomach, and lung squamous cell carcinomas, small cell lung cancer, large-cell neuroendocrine lung cancer, hepatocellular carcinoma, and malignant melanoma. In a retrospective study with 88 LM patients, cancer cells were detected in 80 out of the 88 CSF samples. In the comparative study with 45 LM patients, the initial detection rate of the Thinprep method was significantly higher than that of the Cytospin method (73.3% vs. 57.8%, P<0.01). The cell morphology was better preserved and subcellular structures were clearer using the Thinprep method, compared to the Cytospin method.

Conclusions

The Thinprep method is more sensitive and suitable for LM diagnosis in CSF in patients with malignant solid tumors than the Cytospin method. The Thinprep method may facilitate primary tumor detection and help design early treatment regimens for LM patients with tumors of unknown primary origin.  相似文献   
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