全文获取类型
收费全文 | 7623篇 |
免费 | 451篇 |
国内免费 | 11篇 |
出版年
2012年 | 914篇 |
2011年 | 986篇 |
2010年 | 126篇 |
2009年 | 77篇 |
2008年 | 784篇 |
2007年 | 721篇 |
2006年 | 669篇 |
2005年 | 630篇 |
2004年 | 589篇 |
2003年 | 484篇 |
2002年 | 435篇 |
2001年 | 314篇 |
2000年 | 409篇 |
1999年 | 162篇 |
1998年 | 16篇 |
1997年 | 14篇 |
1996年 | 15篇 |
1995年 | 14篇 |
1994年 | 11篇 |
1993年 | 11篇 |
1992年 | 21篇 |
1991年 | 9篇 |
1990年 | 10篇 |
1989年 | 13篇 |
1988年 | 10篇 |
1986年 | 6篇 |
1985年 | 7篇 |
1983年 | 6篇 |
1980年 | 6篇 |
1959年 | 28篇 |
1958年 | 44篇 |
1957年 | 30篇 |
1956年 | 46篇 |
1955年 | 47篇 |
1954年 | 40篇 |
1953年 | 41篇 |
1952年 | 47篇 |
1951年 | 44篇 |
1950年 | 29篇 |
1949年 | 30篇 |
1948年 | 15篇 |
1947年 | 6篇 |
1946年 | 15篇 |
1945年 | 6篇 |
1943年 | 6篇 |
1942年 | 8篇 |
1939年 | 10篇 |
1937年 | 6篇 |
1936年 | 7篇 |
1935年 | 6篇 |
排序方式: 共有8085条查询结果,搜索用时 140 毫秒
151.
The effects of S-carboxymethylcysteine and N-acetylcysteine on the adherence of Moraxella catarrhalis to human pharyngeal epithelial cells 总被引:3,自引:0,他引:3
We investigated the effects of two mucoregulating drugs, S-carboxymethylcysteine (S-CMC) and N-acetylcysteine (NAC), on the attachment of Moraxella catarrhalis (M. catarrhalis) to pharyngeal epithelial cells. The attachment of M. catarrhalis decreased (33-57%) significantly (P<0.01) in a dose-dependent manner in cells treated with mucoregulating drugs as compared to the control. There was a significant (P<0.01) decrease (35-45%) in the attachment of M. catarrhalis to pharyngeal cells after oral administration of S-CMC. By electron microscopic observation, it was found that there was a fine, granular, electron-dense, ruthenium red-positive layer on the surface of pharyngeal epithelial cells; this layer was absent on cell surfaces treated with mucoregulating drugs. Possibly, this layer contained the portion of M. catarrhalis receptor which is responsible for the attachment of this bacteria to pharyngeal epithelial cells. From the above results, it may be concluded that one of the mechanisms of mucoregulating drugs to decrease the episode of respiratory infections in patients with chronic respiratory diseases is by inhibiting the attachment of bacteria to the upper respiratory tract. 相似文献
152.
AIMS: This study addresses the inducibility of barotolerance by preincubation of Lactobacillus sanfranciscensis DSM 20451T under various sublethal stress conditions. METHODS AND RESULTS: Stress conditions which reduce the growth rate of L. sanfranciscensis DSM 20451T to 10% of its maximum were determined. These conditions were met at 43, 12.5 degrees C, a pH value of 3.7, 1.9% NaCl, or 80 MPa respectively. In contrast to heat preincubation, other prestresses, including salt, cold and pressure led to an increase of barotolerance by hydrostatic pressure of 300 MPa for 30 min. Stationary-phase cells also showed an increased barotolerance. Sublethal pressure leads to enhanced heat tolerance. CONCLUSIONS: Stress response to salt, low temperature and acidic pH as well as starvation overlap with that one to high pressure by inducing barotolerance. SIGNIFICANCE AND IMPACT OF THE STUDY: Inactivation of bacteria by high pressure treatment is influenced by their history which modulates barotolerance. Mechanisms of barotolerance appear different from heat shock defence. 相似文献
153.
154.
Brk activates rac1 and promotes cell migration and invasion by phosphorylating paxillin 总被引:5,自引:1,他引:4
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Chen HY Shen CH Tsai YT Lin FC Huang YP Chen RH 《Molecular and cellular biology》2004,24(24):10558-10572
Brk (for breast tumor kinase) is a nonreceptor tyrosine kinase containing SH3, SH2, and tyrosine kinase catalytic domains. Brk was originally identified from a human metastatic breast tumor, and its overexpression is frequently observed in breast cancer and several other cancer types. However, the molecular mechanism by which this kinase participates in tumorigenesis remains poorly characterized. In the present study, we not only identified paxillin as the binding partner and substrate of Brk but also discovered a novel signaling pathway by which Brk mediates epidermal growth factor (EGF)-induced paxillin phosphorylation. We show that EGF stimulation activates the catalytic activity of Brk, which in turn phosphorylates paxillin at Y31 and Y118. These phosphorylation events promote the activation of small GTPase Rac1 via the function of CrkII. Through this pathway, Brk is capable of promoting cell motility and invasion and functions as a mediator of EGF-induced migration and invasion. In accordance with these functional roles, Brk translocates to membrane ruffles, where it colocalizes with paxillin during cell migration. Together, our findings identify novel signaling and biological roles of Brk and indicate the first potential link between Brk and metastatic malignancy. 相似文献
155.
Two inhibitors, aviglycine and propargylglycine, were tested for their ability to suppress methionine synthesis thus inhibit
conidial germination and mycelial growth of Czapek-Dox liquid medium grown Fusarium oxysporum f. sp. luffae
μM. The linear inhibition range for mycelial growth was about 7.6–762.9 μM. Although aviglycine did not completely inhibit both conidial germination and mycelial growth, it showed significant inhibitory
effect at 1.5 μM. The inhibition range for propargylglycine against conidial germination and mycelial growth were from 0.08 to 8841 μM and from 0.8 to 884.1 μM, respectively. Propargylglycine inhibited conidial germination and mycelial growth at a concentration of 8841 μM. The EC50 values of aviglycine were 1 μM for conidial growth and 122 μM for mycelial growth, and the EC50 values of propargylglycine were 47.7 μM for conidial growth and 55.6 μM for mycelial growth. Supplement of methionine released inhibition of aviglycine or propargylglycine to conidial germination.
In addition, a mixture of aviglycine (1.5 μM) and propargylglycine (8841 μM) showed additive inhibitive effect than applied alone on 10 isolates. From these results, both aviglycine and propargylglycine
exhibited inhibitory activity, and suggest that they can provide potential tools to design novel fungicide against fungal
pathogens. 相似文献
156.
157.
158.
Interaction of human and bacterial AlkB proteins with DNA as probed through chemical cross-linking studies 总被引:2,自引:1,他引:1
The Escherichia coli AlkB protein was recently found to repair cytotoxic DNA lesions 1-methyladenine and 3-methylcytosine by using a novel iron-catalyzed oxidative demethylation mechanism. Three human homologs, ABH1, ABH2 and ABH3, have been identified, and two of them, ABH2 and ABH3, were shown to have similar repair activities to E.coli AlkB. However, ABH1 did not show any repair activity. It was suggested that ABH3 prefers single-stranded DNA and RNA substrates, whereas AlkB and ABH2 can repair damage in both single- and double-stranded DNA. We employed a chemical cross-linking approach to probe the structure and substrate preferences of AlkB and its three human homologs. The putative active site iron ligands in these proteins were mutated to cysteine residues. These mutant proteins were used to cross-link to different DNA probes bearing thiol-tethered bases. Disulfide-linked protein–DNA complexes can be trapped and analyzed by SDS–PAGE. Our results show that ABH2 and ABH3 have structural and functional similarities to E.coli AlkB. ABH3 shows preference for the single-stranded DNA probe. ABH1 failed to cross-link to the probes tested. This protein, unlike other AlkB proteins, does not seem to interact with DNA in its E.coli expressed form. 相似文献
159.
A three-fluorophore FRET assay for high-throughput screening of small-molecule inhibitors of ribosome assembly 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
In one of the first steps of prokaryotic ribosome assembly, the ribosomal protein S15 binds to a three-way junction in the central domain of the 16S rRNA. Binding causes a conformational change that is required for subsequent binding events. Using a novel fluorescence resonance energy transfer assay with three fluorophores, two on the RNA and one on the S15 protein, small-molecule libraries can be screened for potential inhibitors of this initial step in ribosome assembly. The employment of three fluorophores allows both the conformational change of the RNA and the binding of S15 to be monitored in a single assay. 相似文献
160.
Estrogen (17beta-estradiol, or E2) reduces systolic blood pressure (SBP) increment and increases aortic cyclic guanosine monophosphate (cGMP) in male spontaneously hypertensive rats (SHRs). It is unknown, however, whether the E2-enhanced aortic cGMP is essential for the BP-lowering effect or not. Nomega-nitro-L-arginine-methyl ester (L-NAME), an L-arginine analogue and nitric oxide (NO) synthase inhibitor, significantly increases SBP and decreases aortic cGMP in male SHRs. We thus treated male SHRs with vehicle (corn oil) or E2 (s.c, 2 mg/kg/week) with or without L-NAME (20 mg/dl in the drinking water). SBP was measured weekly. Plasma nitrate/nitrite (NOx) concentrations and aortic cGMP levels were all measured at the end of the study. We found that SBP increment was significantly higher in L-NAME group, compared with the controls, and that E2 treatment reduced this L-NAME effect. Plasma 4NOx concentrations were not significantly different among different groups. Basal and acetylcholine-induced aortic cGMP, but not sodium nitroprusside-induced cGMP, were significantly lower in L-NAME group, compared with the controls. E2 co-administration did not modify L-NAME-induced aortic cGMP decrease. These data indicate that E2-induced BP-lowering effect in L-NAME treated male SHRs is not closely associated with the enhancement of vascular cGMP. 相似文献