全文获取类型
收费全文 | 584篇 |
免费 | 47篇 |
出版年
2021年 | 6篇 |
2018年 | 7篇 |
2017年 | 4篇 |
2016年 | 12篇 |
2015年 | 18篇 |
2014年 | 16篇 |
2013年 | 20篇 |
2012年 | 37篇 |
2011年 | 23篇 |
2010年 | 26篇 |
2009年 | 15篇 |
2008年 | 29篇 |
2007年 | 32篇 |
2006年 | 31篇 |
2005年 | 19篇 |
2004年 | 28篇 |
2003年 | 24篇 |
2002年 | 26篇 |
2001年 | 9篇 |
2000年 | 5篇 |
1999年 | 5篇 |
1998年 | 5篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 7篇 |
1992年 | 4篇 |
1986年 | 5篇 |
1984年 | 6篇 |
1983年 | 7篇 |
1982年 | 9篇 |
1981年 | 5篇 |
1980年 | 7篇 |
1977年 | 8篇 |
1965年 | 5篇 |
1939年 | 3篇 |
1937年 | 4篇 |
1936年 | 4篇 |
1935年 | 8篇 |
1934年 | 3篇 |
1933年 | 3篇 |
1932年 | 5篇 |
1931年 | 6篇 |
1930年 | 7篇 |
1929年 | 11篇 |
1927年 | 3篇 |
1925年 | 3篇 |
1897年 | 3篇 |
1896年 | 3篇 |
1892年 | 3篇 |
排序方式: 共有631条查询结果,搜索用时 15 毫秒
31.
32.
Mazza CB Rege K Breneman CM Sukumar N Dordick JS Cramer SM 《Biotechnology and bioengineering》2002,78(1):60-72
The stability and structure of protein-containing water-in-oil (w/o) microemulsions were investigated by using the large protein immunoglobulin G (IgG, MW 155,000) in a mixture comprised of brine, sulfosuccinic acid bis [2-ethylhexyl]ester (sodium salt), and isooctane. We explored factors affecting the initial uptake of IgG into the w/o microemulsion and its subsequent release to a solid (precipitate) phase, and the kinetics of the latter process. Influences of such parameters as pH, ionic strength, and protein concentration on the solubilization and precipitation of bovine IgG in the organic phase are described. The structure and dynamics in microemulsions containing bovine IgG were probed by using dynamic light scattering, and it was found that the presence of IgG in the microemulsion induced strong attractive forces between the droplets. Based on results obtained by using these various experimental approaches, a model for protein solubilization and release is proposed. In this model, we propose the formation of clusters within which bovine IgG resides and which substantially slow the kinetics of protein release from the droplets to the precipitate phase. 相似文献
33.
Self-injurious behavior (SIB) is an untreatable and often life-threatening problem among individuals with developmental disorders, especially those diagnosed with autism. Functioning, relationships and processing of the proopiomelanocortin (POMC) system are "uncoupled" in subgroups of self-injuring individuals resulting in different ratios of ACTH and opioids in the bloodstream, particularly under conditions of stress. In this study, relations between SIB and POMC were evaluated in a multi-year study of the largest prospective sample studied to date. Observations were collected on palmtop computers for 45 treatment-resistant patients who exhibited chronic SIB. Behavior of each subject was observed in natural settings without disruption or intrusion, for continuous, 2.5-h periods, two times a day (morning and afternoon), 4 days a week for two consecutive weeks, for a total of 40 h/subject. Blood was collected in the morning, late afternoon and immediately after an SIB episode on two separate occasions separated by at least 6 months. Levels of beta-endorphin (beta E) and ACTH were assayed by RIA. We discovered that the SIB was the best predictor of subsequent SIB. Moreover, the majority of subjects exhibited this contagious pattern of SIB. Levels of POMC fragments were reliable over a 6- to 9-month period. Subjects exhibiting POMC disregulation characterized by high morning levels of beta E had the highest transitional probabilities of SIB (i.e. contagious patterns; F=8.17, P<0.01). These findings suggest that subjects with "contagious" SIB may represent a behavioral phenotype associated with disregulated expression of the POMC gene. 相似文献
34.
Chai W Breitenbucher JG Kwok A Li X Wong V Carruthers NI Lovenberg TW Mazur C Wilson SJ Axe FU Jones TK 《Bioorganic & medicinal chemistry letters》2003,13(10):1767-1770
Continued exploration of the SAR around the lead imidazopyridine histamine H(3) antagonist 1 has led to the discovery of several related series of heterocyclic histamine H(3) antagonists. The synthesis and SAR of indolizine, indole and pyrazolopyridine based compounds are now described. 相似文献
35.
Ribosomal DNA from eight species of microsporidians infecting fish have been sequenced. Seven of these species infect the skeletal muscle of fish ( Pleistophora spp.) and one species infects migratory mesenchyma cells ( Glugea anomala ). These sequences, in addition to other available microsporidian rDNA sequences from a broad range of host taxa, have been used in phylogenetic analysis. This analysis revealed that muscle-infecting microsporidians from fish are a polyphyletic group, indicating that characters supposed to be important in the classification of the genus Pleistophora have to be re-evaluated. One character that probably has a polyphyletic origin is the amorphous coat, which has been extensively used in the definition of this genus. Furthermore, our results showed that the insect parasitizing Pleistophora spp. are not related to the true pleistophorans parasitic in skeletal muscle of fish. Phylogenetic analysis of small subunit rDNA sequences revealed disagreements between the molecular phylogeny and classifications based upon ultrastruclure. Many of the morphological characters claimed to be important in microsporidian classifications appeared to have arisen several times during evolution: for example, the diplokaryon and sporophorous vesicles. 相似文献
36.
Stat3 Activation Is Required for Cellular Transformation by v-src 总被引:30,自引:2,他引:28
Jacqueline F. Bromberg Curt M. Horvath Daniel Besser Wyndham W. Lathem James E. Darnell Jr. 《Molecular and cellular biology》1998,18(5):2553-2558
Stat3 activation has been associated with cytokine-induced proliferation, anti-apoptosis, and transformation. Constitutively activated Stat3 has been found in many human tumors as well as v-abl- and v-src-transformed cell lines. Because of these correlations, we examined directly the relationship of activated Stat3 to cellular transformation and found that wild-type Stat3 enhances the transforming potential of v-src while three dominant negative Stat3 mutants inhibit v-src transformation. Stat3 wild-type or mutant proteins did not affect v-ras transformation. We conclude that Stat3 has a necessary role in v-src transformation. 相似文献
37.
Viviane D. Lima Isabell Graf Curt G. Beckwith Sandra Springer Frederick L. Altice Daniel Coombs Brian Kim Lauren Messina Julio S. G. Montaner Anne Spaulding 《PloS one》2015,10(4)
Background
Annually, 10 million adults transition through prisons or jails in the United States (US) and the prevalence of HIV among entrants is three times higher than that for the country as a whole. We assessed the potential impact of increasing HIV Testing/Treatment/Retention (HIV-TTR) in the community and within the criminal justice system (CJS) facilities, coupled with sexual risk behavior change, focusing on black men-who-have-sex-with-men, 15–54 years, in Atlanta, USA.Methods
We modeled the effect of a HIV-TTR strategy on the estimated cumulative number of new (acquired) infections and mortality, and on the HIV prevalence at the end of ten years. We additionally assessed the effect of increasing condom use in all settings.Results
In the Status Quo scenario, at the end of 10 years, the cumulative number of new infections in the community, jail and prison was, respectively, 9246, 77 and 154 cases; HIV prevalence was 10815, 69 and 152 cases, respectively; and the cumulative number of deaths was 2585, 18 and 34 cases, respectively. By increasing HIV-TTR coverage, the cumulative number of new infections could decrease by 15% in the community, 19% in jail, and 8% in prison; HIV prevalence could decrease by 8%, 9% and 7%, respectively; mortality could decrease by 20%, 39% and 18%, respectively. Based on the model results, we have shown that limited use and access to condoms have contributed to the HIV incidence and prevalence in all settings.Conclusions
Aggressive implementation of a CJS-focused HIV-TTR strategy has the potential to interrupt HIV transmission and reduce mortality, with benefit to the community at large. To maximize the impact of these interventions, retention in treatment, including during the period after jail and prison release, and increased condom use was vital for decreasing the burden of the HIV epidemic in all settings. 相似文献38.
Gabriela E. Davey Bin Wu Yuancai Dong Uttam Surana Curt A. Davey 《Nucleic acids research》2010,38(6):2081-2088
DNA stretching in the nucleosome core can cause dramatic structural distortions, which may influence compaction and factor recognition in chromatin. We find that the base pair unstacking arising from stretching-induced extreme minor groove kinking near the nucleosome centre creates a hot spot for intercalation and alkylation by a novel anticancer compound. This may have far reaching implications for how chromatin structure can influence binding of intercalator species and indicates potential for the development of site selective DNA-binding agents that target unique conformational features of the nucleosome. 相似文献
39.
Haffner CD Thomson SA Guo Y Petrov K Larkin A Banker P Schaaf G Dickerson S Gobel J Gillie D Condreay JP Poole C Carpenter T Ulrich J 《Bioorganic & medicinal chemistry letters》2010,20(23):6989-6992
We report the synthesis and in vitro activity of a series of novel substituted N-{3-[(1,1-dioxido-1,2-benzothiazol-3-yl)(phenyl)amino]propyl}benzamide analogs. These analogs showed potent inhibitory activity against Kv1.3. Several demonstrated similar potency to the known Kv1.3 inhibitor PAP-1 when tested under the IonWorks patch clamp assay conditions. Two compounds 13i and 13rr were advanced further as potential tool compounds for in vivo validation studies. 相似文献