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排序方式: 共有320条查询结果,搜索用时 15 毫秒
41.
42.
Garner CE Sloan C Sumner SC Burgess J Davis J Etheridge A Parham A Ghanayem BI 《Biology of reproduction》2007,76(3):496-505
1-bromopropane (1-BrP) induces dose- and time-dependent reproductive organ toxicity and reduced sperm motility in rodents. The contribution of cytochrome P4502E1 (CYP2E1) to both 1-BrP metabolism and the induction of male reproductive toxicity was investigated using wild-type (WT) and Cyp2e1-/- mice. In gas uptake inhalation studies, the elimination half-life of [1,2,3-(13)C]-1-BrP was longer in Cyp2e1-/- mice relative to WT (3.2 vs. 1.3 h). Urinary metabolites were identified by 13C nuclear magnetic resonance. The mercapturic acid of 1-bromo-2-hydroxypropane (2OHBrP) was the major urinary metabolite in WT mice, and products of conjugation of 1-BrP with glutathione (GSH) were insignificant. The ratio of GSH conjugation to 2-hydroxylation increased 5-fold in Cyp2e1-/- mice relative to WT. After 1-BrP exposure, hepatic GSH was decreased by 76% in WT mice vs. 47% in Cyp2e1-/- mice. Despite a 170% increase in 1-BrP exposure in Cyp2e1-/- vs. WT mice, sperm motility in exposed Cyp2e1-/- mice did not change relative to unexposed matched controls. This suggests that metabolites produced through CYP2E1-mediated oxidation may be responsible for 1-BrP-induced sperm toxicity. Both 1-BrP and 2OHBrP inhibited the motility of sperm obtained from WT mice in vitro. However, only 2OHBrP reduced the motility of sperm obtained from Cyp2e1-/- mice in vitro, suggesting that conversion of parent compound to 2OHBrP within the spermatozoa may contribute, at least in part, to reduced motility. Overall, these data suggest that metabolism of 1-BrP is mediated in part by CYP2E1, and activation of 1BrP via this enzyme may contribute to the male reproductive toxicity of this chemical. 相似文献
43.
WenFeng He Gang Yang Shuya Liu Mazaher Maghsoudloo Marzieh Dehghan Shasaltaneh Parham Jabbarzadeh Kaboli Cuiwei Zhang JingHeng Zhang Maliheh Entezari Saber Imani QingLian Wen 《Translational oncology》2021,14(12)
This study aimed to identify a novel disease-associated differentially co-expressed mRNA-microRNA (miRNA) that is associated with vasculogenic mimicry (VM) and epithelial-to-mesenchymal transition (EMT) network at different stages of melanoma. By applying weighted gene co-expression network analysis, we constructed a VM+EMT biological network with the available microarray dataset downloaded from a public database. Quantitative real-time PCR, immunohistochemical staining, and CD31-periodic acid solution dual staining were performed to confirm the expression of genes associated with EMT and VM formation in subjects with malignant melanoma (n = 18) and primary melanoma (n = 13) and in healthy subjects (n = 10). Our findings suggested that phosphatidylserine-specific phospholipase A1-alpha (PLA1A) and dermokine (DMKN) genes function as oncogenes that trigger VM and EMT processes during melanomagenesis on interaction with miR-370, miR-563, and miR-770–5p. PLA1A and DMKN genes can be considered potential VM+EMT network-based diagnostic biomarkers for distinguishing between melanoma patients. We postulate that a network with altered PLA1A/miR-563 and DMNK/miR-770–5p/miR-370 may contribute to melanomagenesis by triggering the EMT signaling pathway and VM formation. This study provides a potentially valuable approach for the early diagnosis and prognosis of melanoma progression. 相似文献
44.
Reuben Thomas Julia M Gohlke Geffrey F Stopper Frederick M Parham Christopher J Portier 《Genome biology》2009,10(4):R44-15
A method is proposed that finds enriched pathways relevant to a studied condition using the measured molecular data and also the structural information of the pathway viewed as a network of nodes and edges. Tests are performed using simulated data and genomic data sets and the method is compared to two existing approaches. The analysis provided demonstrates the method proposed is very competitive with the current approaches and also provides biologically relevant results. 相似文献
45.
California is a biodiversity hotspot facing unbridled human population growth, especially in Central California. One of the
poorly known, sensitive species in this area is the California legless lizard (Anniella pulchra), a fossorial worm-like reptile. We report mt and nuDNA sequences from 69 museum-vouchered samples of Anniella (A. pulchra and its sister species A. geronimensis) from 48 localities. Our genetic survey reveals substantially more genetic diversity within A. pulchra than previously reported. Our two independently evolving markers (mt and nuDNA) reveal five major lineages of A. pulchra. Two of the five major lineages of A. pulchra correspond to a north-south split found in other widespread California reptiles. These northern and southern clades also
correspond to a previous study showing variation in chromosomal number. Unlike most other Californian reptiles, A. pulchra has major genetic lineages that are endemic to Central California including two that are endemic to the San Joaquin Valley
and Carrizo Plain. Although A. pulchra is threatened throughout its range, the distinct San Joaquin lineages are seriously imperiled by urban sprawl. Some of the
localities for the newly recognized genetic lineages have already been destroyed by development. 相似文献
46.
Evaluation of acetylcholinesterase and carbonic anhydrase inhibition profiles of 1,2,3,4,6‐pentasubstituted‐4‐hydroxy‐cyclohexanes 下载免费PDF全文
Umit M. Kocyigit Parham Taslimi Hayreddin Gezegen İlhami Gulçin Mustafa Ceylan 《Journal of biochemical and molecular toxicology》2017,31(9)
Carbonic anhydrase (CA; EC 4.2.1.1) is used for remedial purposes for several years, as there is significant focus on expanding more new activators (CAAs) and high affinity inhibitors. Alzheimer′s disease and other similar ailments such as dementia and vascular dementia with Lewy bodies reduce cholinergic activity in the important areas involved in cognition and memory. Prevalent drugs for the symptomatic therapy of dementia are significant in increasing the associated cholinergic deficiency by inhibiting acetylcholinesterase (AChE). These six‐membered carbocycles showed nice inhibitory action against AChE and human carbonic anhydrase (hCA) II and I isoforms. The hCA I, II, and AChE were efficiently inhibited by these molecules, with Ki values in the range of 6.70–35.85 nM for hCA I, 18.77–60.84 nM for hCA II, and 0.74–4.60 for AChE, respectively. 相似文献
47.
Halise Inci Gul Parham Taslimi Ilhami Gulcin Claudiu T. Supuran 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):189-192
4-(3-(4-Substituted-phenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl) benzenesulfonamides (9–16) were successfully synthesized and their chemical structures were confirmed by 1H NMR, 13C NMR, and HRMS spectra. Carbonic anhydrase I and II inhibitory effects of the compounds were investigated. Ki values of the compounds were in the range of 316.7?±?9.6–533.1?±?187.8?nM towards hCA I and 412.5?±?115.4–624.6?±?168.2?nM towards hCA II isoenzymes. While Ki values of the reference compound Acetazolamide were 278.8?±?44.3?nM and 293.4?±?46.4?nM towards hCA I and hCA II izoenzymes, respectively. Compound 14 with bromine and compound 13 with fluorine substituents can be considered as the leader compounds of the series because of the lowest Ki values in series to make further detailed carbonic anhydrase inhibiton studies. 相似文献
48.
Human killer cell immunoglobulin-like receptors (KIR) recognize A3/11, Bw4, C1, and C2 epitopes carried by mutually exclusive
subsets of human leukocyte antigen (HLA)-A, -B, and -C allotypes. Chimpanzee and orangutan have counterparts to HLA-A, -B,
and -C, and KIR that recognize the A3/11, Bw4, C1, and C2 epitopes, either individually or in combination. Because rhesus
macaque has counterparts of HLA-A and -B, but not HLA-C, we expected that rhesus KIR would better recognize HLA-A and -B,
than HLA-C. Comparison of the interactions of nine rhesus KIR3D with 95 HLA isoforms, showed the KIR have broad specificity
for HLA-A, -B, and -C, but vary in avidity. Considering both the strength and breadth of reaction, HLA-C was the major target
for rhesus KIR, followed by HLA-B, then HLA-A. Strong reactions with HLA-A were restricted to the minority of allotypes carrying
the Bw4 epitope, whereas strong reactions with HLA-B partitioned between allotypes having and lacking Bw4. Contrasting to
HLA-A and -B, every HLA-C allotype bound to the nine rhesus KIR. Sequence comparison of high- and low-binding HLA allotypes
revealed the importance of polymorphism in the helix of the α1 domain and the peptide-binding pockets. At peptide position 9, nonpolar residues favor binding to rhesus KIR, whereas charged
residues do not. Contrary to expectation, rhesus KIR bind more effectively to HLA-C, than to HLA-A and -B. This property is
consistent with major histocompatibility complex (MHC)-C having evolved in hominids to be a generally superior ligand for
KIR than MHC-A and MHC-B. 相似文献
49.
Minoo P Chughtai N Campiglio M Stein-Gerlach M Lebrun JJ Ullrich A Ali S 《Cellular signalling》2003,15(3):319-326
SHP-2, a cytosolic protein tyrosine phosphatase with two SH2 domains and multiple tyrosine phosphorylation sites, contributes to signal transduction as an enzyme and/or adaptor molecule. Here we demonstrate that prolactin (PRL) stimulation of the PRL-responsive Nb2 cells, a rat lymphoma cell line, and T47D cells, a human breast cancer cell line, lead to the complex formation of SHP-2 and growth factor receptor-bound protein-2 (grb2). Using transient co-overexpression studies of the prolactin receptor (PRLR) and several tyrosine to phenylalanine mutants of SHP-2, we show that grb2 associates with SHP-2 through the C-terminal tyrosine residues of SHP-2, Y(546) and Y(584). Furthermore, in this study, we found a highly phosphorylated, 29-kDa protein (p29), a substrate of SHP-2. The recruitment of p29 to SHP-2 requires the carboxy-terminal tyrosine residues of SHP-2 (Y(546) and Y(584)). Together, our results indicate that SHP-2 may function as an adaptor molecule downstream of the PRLR and highlight a new recruitment mechanism of SHP-2 substrates. 相似文献
50.