全文获取类型
收费全文 | 358篇 |
免费 | 38篇 |
出版年
2020年 | 5篇 |
2018年 | 5篇 |
2017年 | 4篇 |
2016年 | 6篇 |
2015年 | 6篇 |
2014年 | 7篇 |
2013年 | 6篇 |
2012年 | 11篇 |
2011年 | 17篇 |
2010年 | 9篇 |
2009年 | 8篇 |
2008年 | 23篇 |
2007年 | 11篇 |
2006年 | 12篇 |
2005年 | 17篇 |
2004年 | 8篇 |
2003年 | 5篇 |
2002年 | 10篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1998年 | 8篇 |
1997年 | 9篇 |
1996年 | 6篇 |
1992年 | 6篇 |
1991年 | 8篇 |
1990年 | 7篇 |
1989年 | 9篇 |
1988年 | 14篇 |
1987年 | 8篇 |
1986年 | 11篇 |
1985年 | 11篇 |
1984年 | 5篇 |
1983年 | 10篇 |
1982年 | 4篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 8篇 |
1978年 | 10篇 |
1977年 | 7篇 |
1975年 | 2篇 |
1974年 | 6篇 |
1973年 | 7篇 |
1972年 | 11篇 |
1971年 | 3篇 |
1970年 | 3篇 |
1969年 | 9篇 |
1968年 | 5篇 |
1967年 | 3篇 |
1965年 | 2篇 |
1948年 | 3篇 |
排序方式: 共有396条查询结果,搜索用时 15 毫秒
121.
Masha T. van der Sande Helge Bruelheide Wayne Dawson Jürgen Dengler Franz Essl Richard Field Sylvia Haider Mark van Kleunen Holger Kreft Joern Pagel Jan Pergl Oliver Purschke Petr Pyek Patrick Weigelt Marten Winter Fabio Attorre Isabelle Aubin Erwin Bergmeier Milan Chytrý Matteo Dainese Michele De Sanctis Jaime Fagundez Valentin Golub Greg R. Guerin Alvaro G. Gutirrez Ute Jandt Florian Jansen Borja Jimnez‐Alfaro Jens Kattge Elizabeth Kearsley Stefan Klotz Koen Kramer Marco Moretti Ülo Niinemets Robert K. Peet Josep Penuelas Petr Petík Peter B. Reich Brody Sandel Marco Schmidt Maria Sibikova Cyrille Violle Timothy J. S. Whitfeld Thomas Wohlgemuth Tiffany M. Knight 《Global Ecology and Biogeography》2020,29(2):281-294
122.
Kevin Hannigan Shridhar S. Kulkarni Volodymyr G. Bdzhola Andriy G. Golub Sergiy M. Yarmoluk Tanaji T. Talele 《Bioorganic & medicinal chemistry letters》2013,23(21):5790-5794
Poly(ADP-ribose)polymerase-1 (PARP-1) is an abundant and ubiquitous chromatin-bound nuclear protein. PARP-1, a DNA repair enzyme, has been in the limelight as a chemotherapeutic target. In this study, we demonstrated the successful use of structure-based virtual screening to identify inhibitors of PARP-1 from Otava databases comprised of nearly 260,000 compounds. Five novel inhibitors belonging to thienopyrimidinone, isoquinolinoquinazolinone, pyrroloquinazolinone, and cyclopentenothienopyrimidinone scaffolds revealed inhibitory potencies with IC50 values ranged from 9.57 μM to 0.72 μM. Structural features relevant to the activity of these novel compounds within the active site of PARP-1 are discussed in detail and will guide future SAR investigation on these scaffolds. 相似文献
123.
Golub AG Bdzhola VG Kyshenia YV Sapelkin VM Prykhod'ko AO Kukharenko OP Ostrynska OV Yarmoluk SM 《Molecular and cellular biochemistry》2011,356(1-2):107-115
Serine/threonine protein kinase CK2 controls vast variety of fundamental processes in cell life; however, despite long period of study, its functional role is not completely determined. CK2 has a significant pathogenic potential and its activity is strictly associated with the development of various kinds of disorders. There are a growing number of facts that inhibitors of CK2 could be used as pharmaceutical agents for the cancer treatment, viral infections, and inflammatory diseases. In this article, we report structural and biological data on the novel synthetic flavonol derivatives, 3-hydroxy-4'-carboxyflavones, possessing a high inhibitory activity toward CK2. With the aid of combinatorial organic synthesis, molecular modeling techniques and biochemical in vitro tests, we studied the structure-activity relationships of flavonol derivatives and developed binding model describing their key intermolecular interactions with the CK2 ATP-binding site. Obtained data show that the synthetic 3-hydroxy-4'-carboxyflavones possess the highest activity among flavonol inhibitors of CK2 known till date. 相似文献
124.
Golub KW Smith AD Hollister EB Gentry TJ Holtzapple MT 《Bioresource technology》2011,102(8):5066-5075
This study evaluated anaerobic mixed-acid countercurrent fermentations in both strict S (minimal oxygen) and relaxed R (high oxygen) conditions. In relaxed fermentations, filter solids and liquids were exposed to air for 90 min every 56 h. The total acid concentrations for four-stage trains were 23.0 (4S) and 22.1 (4R) g/LLiq, and for one-stage trains were 17.2 (1S) and 18.4 (1R) g/LLiq. The strict and relaxed trains had statistically similar exit yields. The strict trains had significantly more high-molecular-weight carboxylic acids. The relaxed trains had slightly higher conversion and slightly lower selectivity, but not significantly. Air exposure had no significant effect on the bacterial profiles of the strict and relaxed fermentations. For all fermentations, the most abundant bacterial genus was Prevotella, a strict anaerobe. This study shows that the mixed-culture community is oxygen tolerant because it maintains fermentation performance during oxygen-induced stress. 相似文献
125.
Golub AS Barker MC Pittman RN 《American journal of physiology. Heart and circulatory physiology》2007,293(2):H1097-H1106
A scanning phosphorescence quenching microscopy technique, designed to prevent accumulated O(2) consumption by the method, was applied to Po(2) measurements in mesenteric tissue. In an attempt to further increase the accuracy of the measurements, albumin-bound probe was topically applied to the tissue and an objective-mounted pressurized bag was used to reduce the oxygen transport bypass through the thin layer of fluid over the mesentery. Po(2) was measured at multiple sites perpendicular to the blood/wall interface in the vicinity of 84 mesenteric arterioles (7-39 microm in diameter) at distances of 5, 15, 30, 60, 120, and 180 microm in seven anesthetized Sprague-Dawley rats, thereby creating Po(2) profiles. Interstitial Po(2) above and immediately beside arterioles was found to agree with known intravascular values. No significant difference in Po(2) profiles was found between small and large arterioles, indicating a small longitudinal Po(2) gradient in the precapillary mesenteric microvasculature. In addition, the Po(2) profiles were used to calculate oxygen consumption in the mesenteric tissue (56-65 nl O(2) x cm(-3) x s(-1)). Correction of these values for contamination with ambient oxygen yielded an oxygen consumption rate of 60-68 nl O(2) x cm(-3) x s(-1), the maximal limit for consumption in the mesentery. The results were compared with measurements made by other workers in regard to the employed techniques. 相似文献
126.
127.
Douglas S. Goodin Michael Corwin David Kaufman Howard Golub Shoshana Reshef Mark J. Rametta Volker Knappertz Gary Cutter Dirk Pleimes 《PloS one》2014,9(8)
Background
Information on causes of death (CODs) for patients with multiple sclerosis (MS) in the United States is sparse and limited by standard categorizations of underlying and immediate CODs on death certificates. Prior research indicated that excess mortality among MS patients was largely due to greater mortality from infectious, cardiovascular, or pulmonary causes.Objective
To analyze disease categories in order to gain insight to pathways, which lead directly to death in MS patients.Methods
Commercially insured MS patients enrolled in the OptumInsight Research database between 1996 and 2009 were matched to non-MS comparators on age/residence at index year and sex. The cause most-directly leading to death from the death certificate, referred to as the “principal” COD, was determined using an algorithm to minimize the selection of either MS or cardiac/pulmonary arrest as the COD. Principal CODs were categorized into MS, cancer, cardiovascular, infectious, suicide, accidental, pulmonary, other, or unknown. Infectious, cardiovascular, and pulmonary CODs were further subcategorized.Results
30,402 MS patients were matched to 89,818 controls, with mortality rates of 899 and 446 deaths/100,000 person-years, respectively. Excluding MS, differences in mortality rate between MS patients and non-MS comparators were largely attributable to infections, cardiovascular causes, and pulmonary problems. Of the 95 excessive deaths (per 100,000 person-years) related to infectious causes, 41 (43.2%) were due to pulmonary infections and 45 (47.4%) were attributed to sepsis. Of the 46 excessive deaths (per 100,000 person-years) related to pulmonary causes, 27 (58.7%) were due to aspiration. No single diagnostic entity predominated for the 60 excessive deaths (per 100,000 person-years) attributable to cardiac CODs.Conclusions
The principal COD algorithm improved on other methods of determining COD in MS patients from death certificates. A greater awareness of the common CODs in MS patients will allow physicians to anticipate potential problems and, thereby, improve the care that they provide. 相似文献128.
L Herrmann IA Ionescu K Henes Y Golub NX Wang DR Buell F Holsboer CT Wotjak U Schmidt 《PloS one》2012,7(8):e42603
Despite intensive research efforts, the molecular pathogenesis of posttraumatic stress disorder (PTSD) and especially of the hippocampal volume loss found in the majority of patients suffering from this anxiety disease still remains elusive. We demonstrated before that trauma-induced hippocampal shrinkage can also be observed in mice exhibiting a PTSD-like syndrome. Aiming to decipher the molecular correlates of these trans-species posttraumatic hippocampal alterations, we compared the expression levels of a set of neurostructural marker proteins between traumatized and control mice at different time points after their subjection to either an electric footshock or mock treatment which was followed by stressful re-exposure in several experimental groups. To our knowledge, this is the first systematic in vivo study analyzing the long-term neuromolecular sequelae of acute traumatic stress combined with re-exposure. We show here that a PTSD-like syndrome in mice is accompanied by a long-lasting reduction of hippocampal synaptic proteins which interestingly correlates with the strength of the generalized and conditioned fear response but not with the intensity of hyperarousal symptoms. Furthermore, we demonstrate that treatment with the serotonin reuptake inhibitor (SSRI) fluoxetine is able to counteract both the PTSD-like syndrome and the posttraumatic synaptic protein loss. Taken together, this study demonstrates for the first time that a loss of hippocampal synaptic proteins is associated with a PTSD-like syndrome in mice. Further studies will have to reveal whether these findings are transferable to PTSD patients. 相似文献
129.
Martić S Tackenburg S Bilokin Y Golub A Bdzhola V Yarmoluk S Kraatz HB 《Analytical biochemistry》2012,421(2):617-621
An electrochemical method based on the bioorganometallic Fc-ATP cosubstrate for kinase-catalyzed phosphorylation reactions was used for monitoring casein kinase 2 (CK2) phosphorylations in the absence and presence of five indole/quinolone-based potential inhibitors. Fc-phosphorylation of immobilized peptide RRRDDDSDDD on Au surfaces resulted in a current density at approximately 460 ± 10 mV. An electrochemical redox signal was significantly decreased in the presence of inhibitors. In addition, the electrochemical signal was concentration dependent with respect to the potential inhibitors 1 to 5, which proved to be viable CK2 drug targets with estimated IC50 values in the nanomolar range. 相似文献
130.
BENOÎT O. L. DEMARS JACQUELINE M. POTTS MICHÈLE TRÉMOLIÈRES GABRIELLE THIÉBAUT NATHALIE GOUGELIN VINCENT NORDMANN 《Freshwater Biology》2012,57(8):1745-1759
1. Recent studies have demonstrated that there is generally no unambiguous relationship between plant species composition and specific environmental conditions in rivers. Nevertheless, indices of environmental pressures based on macrophytes are flourishing, because of the requirements of the Water Framework Directive (WFD). 2. We first reviewed nine such indices against 13 criteria for bioindicators. Then, using data from France and England, we tested whether the IBMR (Macrophyte Biological Index for Rivers) and LEAFPACS (predictions and classification system for macrophytes) methods could reliably indicate nutrient and hydromorphological pressures. Finally, we used an improved bootstrapping method to estimate accuracy. 3. Currently, most indices lack ecological meaning for a variety of reasons, including partial sampling (backwaters are excluded); reliance on list of taxa (there are identification difficulties) rather than structure and functions; correlation rather than causation; application within a limited biogeographical area; reliance on ‘expert’ judgement; high precision but poor accuracy; poorly defined reference conditions; lack of independent tests; and an inability to discriminate reliably between the target pressures of interest from confounding background variables. 4. IBMR was a far better indicator of pH (or HCO3‐pCO2) than it was of soluble reactive phosphorus, SRP (or SRP‐NH4). While there was a highly significant correlation between IBMR and SRP after removing the effect of pH, the relationship was weak (r2 = 0.08, n = 215, P < 0.001). 5. LEAFPACS is a multi‐metric method summing up five individual indices, each compliant with the WFD. Its individual metrics were not better correlated with nutrient and hydromorphological pressures (with r2 < 0.1, n = 62, P < 0.05) than was the IBMR. The meaning of the overall metric is questionable. 6. There are problems in determining the precision of the indices, owing to uncertainties in recording, but they are less than the uncertainties in determining accuracy (because species optima and tolerances are sometimes poorly known). 7. Reliable information is needed to improve the state of our rivers. Macrophyte indices are able to detect statistically significant pressures from a large population of sites but cannot be applied at specific sites, as required by the WFD, owing to large uncertainties and low explanatory power. Typically, more than 90% of the variability in macrophyte indices is attributed to factors other than human pressure. The WFD would be better served by a simpler, holistic approach based on our current mechanistic understanding of river processes. These findings are likely to apply also to other taxonomic groups (macroinvertebrates, diatoms, fish) used in the assessment of purported ecological quality and to palaeolimnological measures of reference status. 相似文献