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101.
Michal Bijak Alicja Olejnik Bozena Rokita Agnieszka Morel Angela Dziedzic Elzbieta Miller Joanna Saluk‐Bijak 《Journal of cellular and molecular medicine》2019,23(5):3476-3482
Epidemiological studies indicate a high risk of stroke, heart failure and myocardial infarction in patients with multiple sclerosis, especially in its secondary progressive (SPMS) phase. Some ischaemic events are directly associated with abnormal platelet functions and their prothrombotic activity. Recent reports, including this study, confirm the increased activation of circulating platelets in SPMS, and also show increased platelet reactivity, among other responses, as well as strong aggregation. In this current study, we conducted a comparative analysis of the platelet proteome in SPMS patients and in healthy controls, to demonstrate the quantitative and qualitative differences likely to affect functional changes observed in SPMS. During densitometry evaluation of 2‐D fluorescence difference gel electrophoresis, we observed differences between the electrophoretic patterns of SPMS platelets and the control samples. To determine a detailed characterisation of the proteome changes in the SPMS patients’ blood platelets, in the next stage, we performed mass spectrometry of selected spots and indicated the increased presence of four proteins (fibrinogen, α‐2 macroglobulin, septin‐14 and tubulin β‐1 chain). The most important of these is the increased amount of prothrombotic protein, fibrinogen, which seems to confirm the accuracy of the imaging and potentially explains the increased risk of platelet‐origin thrombotic events. This study provides new knowledge of the potential existence of the molecular mechanisms responsible for the acceleration of the platelet pro‐coagulant function in SPMS. This can help to identify new targets for therapy, which can then be used not only in the second stage of the disease. 相似文献
102.
Michael Jakob Rupar Pawel Golusinski Wojciech Golusinski Michal M. Masternak 《Reports of Practical Oncology and Radiotherapy》2019,24(6):544-550
Human Papillomavirus (HPV) remains one of the most commonly contracted sexually transmitted diseases around the world. There are a multitude of HPV types, some of which may never present any symptoms. Others, however, are considered high-risk types, which increase the chance of the person infected to develop cancer. In recent years, the utilization of nanotechnology has allowed researchers to employ and explore the use of nanoparticles in immunotherapies.The new nanoparticle frontier has opened many doors in this area of research as a form of prevention, diagnosis, and treatment in cancers resulting from HPV. This review will provide a brief background of HPV, its relationship to head and neck cancer (HNC) and present some insight into the field of immunotherapeutic nanoparticles. 相似文献
103.
Strunecký Otakar Kopejtka Karel Goecke Franz Tomasch Jürgen Lukavský Jaromír Neori Amir Kahl Silke Pieper Dietmar H. Pilarski Plamen Kaftan David Koblížek Michal 《Extremophiles : life under extreme conditions》2019,23(1):35-48
Extremophiles - Genotypic and morphological diversity of cyanobacteria in the Rupite hot spring (Bulgaria) was investigated by means of optical microscopy, cultivation, single-cell PCR, and 16S... 相似文献
104.
Rambabu Dakarapu Ramu Errabelli Vijaya L. Manthati Adeniyi Michael Adebesin Deb K. Barma Deepan Barma Victor Garcia Fan Zhang Michal Laniado Schwartzman John R. Falck 《Bioorganic & medicinal chemistry letters》2019,29(19):126616
19-Hydroxyeicosatetraenoic acid (19-HETE, 1), a metabolically and chemically labile cytochrome P450 eicosanoid, has diverse biological activities including antagonism of the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE, 2). A SAR study was conducted to develop robust analogs of 1 with improved in vitro and in vivo efficacy. Analogs were screened in vitro for inhibition of 20-HETE-induced sensitization of rat renal preglomerular microvessels toward phenylephrine and demonstrated to normalize the blood pressure of male Cyp4a14(-/-) mice that display androgen-driven, 20-HETE-dependent hypertension. 相似文献
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108.
The DNA damage response mediator MDC1 directly interacts with the anaphase-promoting complex/cyclosome 总被引:1,自引:0,他引:1
Coster G Hayouka Z Argaman L Strauss C Friedler A Brandeis M Goldberg M 《The Journal of biological chemistry》2007,282(44):32053-32064
MDC1 (NFBD1), a mediator of the cellular response to DNA damage, plays an important role in checkpoint activation and DNA repair. Here we identified a cross-talk between the DNA damage response and cell cycle regulation. We discovered that MDC1 binds the anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase that controls the cell cycle. The interaction is direct and is mediated by the tandem BRCA1 C-terminal domains of MDC1 and the C terminus of the Cdc27 (APC3) subunit of the APC/C. It requires the phosphorylation of Cdc27 and is enhanced after induction of DNA damage. We show that the tandem BRCA1 C-terminal domains of MDC1, known to directly bind the phosphorylated form of histone H2AX (gamma-H2AX), also bind the APC/C by the same mechanism, as phosphopeptides that correspond to the C termini of gamma-H2AX and Cdc27 competed with each other for the binding to MDC1. Our results reveal a link between the cellular response to DNA damage and cell cycle regulation, suggesting that MDC1, known to have a role in checkpoint regulation, executes part of this role by binding the APC/C. 相似文献
109.
Kunej T Wang Z Michal JJ Daniels TF Magnuson NS Jiang Z 《Obesity (Silver Spring, Md.)》2007,15(12):2896-2901
Obesity and type 2 diabetes constitute leading public health problems worldwide. Studies have shown that insulin resistance affiliated with these conditions is associated with skeletal muscle lipid accumulation, while the latter is associated with mitochondrial dysfunctions. However, the initiation and regulation of mitochondrial biogenesis rely heavily on approximately 1000 nuclear-encoded mitochondrial regulatory proteins. In this study, we targeted the ubiquinol-cytochrome c reductase core protein I gene, a nuclear-encoded component of mitochondrial complex III, for its association with subcutaneous fat depth (SFD) and skeletal muscle lipid accumulation (SMLA) using cattle as a model. Four promoter polymorphisms were identified and genotyped on approximately 250 Wagyu x Limousin F2 progeny. Statistical analysis revealed that two completely linked polymorphic sites, g.13487C>T and g.13709G>C (r2 = 1), were significantly associated with both SFD (p < 0.01) and SMLA (p < 0.0001). The difference between TTCC and CCGG haplotypes was 0.178 cm for SFD and 0.624 scores for SMLA. Interestingly, the former haplotype produced higher promoter activities than the latter by 43% to 49% in three cell lines (p < 0.05). In addition to Rett syndrome and breast/ovarian cancer observed in other studies, we report evidence for the first time, to our knowledge, that overexpression of ubiquinol-cytochrome c reductase core protein I might affect mitochondrial morphology and/or physiology and lead to development of obesity and related conditions. 相似文献
110.
Salah Z Maoz M Pokroy E Lotem M Bar-Shavit R Uziely B 《Molecular cancer research : MCR》2007,5(3):229-240
Although ample evidence point to the central involvement of protease activated receptor-1 (PAR1) in tumor progression, little is known about the fate of the tumor when hPar1 is being silenced. We observed that hPar1 antisense clones exhibit low PAR1 levels, attenuated cell proliferation and invasion in vitro, and tumor formation in vivo. These clones showed noticeably reduced paxillin phosphorylation compared with the parental A375SM cells, whereas no change in the integrin levels was noticed. Antisense clones injected into the mice resulted in very few and only occasional small tumors, whereas advanced and vascularized tumors were observed in A375SM cells. The antisense-derived tumor sections expressed active caspase-3, increased terminal deoxynucleotidyl transferase-mediated nick-end labeling staining, and a markedly reduced proliferating cell nuclear antigen level compared with A375SM cell-derived tissue sections. Likewise, ablation of the hPar1 gene in a tetracycline-inducible hPar1 system leads to apoptosis in immature blood vessels, whereas mature vessels were unaffected. The activation of PAR1-induced pAkt/protein kinase B abrogated serum-deprived Bim(EL) induction and also markedly inhibited Bax levels. On the other hand, small interfering RNA silencing of the hPar1 gene induced the expression of Bim(EL), a direct substrate of Akt/protein kinase B and also induced expression of active caspase-9 and caspase-3. These results altogether identify PAR1 as a survival factor that protects cells from undergoing apoptosis. We conclude that whereas PAR1 gene expression correlates with tumor progression, its neutralization effectively initiates an apoptotic pathway leading at least in part to significantly reduced tumor formation. 相似文献