全文获取类型
收费全文 | 199篇 |
免费 | 16篇 |
出版年
2024年 | 1篇 |
2022年 | 2篇 |
2021年 | 5篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2016年 | 4篇 |
2015年 | 8篇 |
2014年 | 20篇 |
2013年 | 15篇 |
2012年 | 13篇 |
2011年 | 16篇 |
2010年 | 10篇 |
2009年 | 8篇 |
2008年 | 11篇 |
2007年 | 5篇 |
2006年 | 8篇 |
2005年 | 12篇 |
2004年 | 7篇 |
2003年 | 13篇 |
2002年 | 7篇 |
2001年 | 4篇 |
2000年 | 7篇 |
1999年 | 9篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有215条查询结果,搜索用时 46 毫秒
1.
—The convulsant action of methyldithiocarbazinate (MDTC), thiocarbohydrazide (TCH) and thiosemicarbazide (TSC) has been studied in mice. The relationship between dose and time to convulsions indicated that MDTC has a dual action and is more potent than TSC. Pretreatment of mice with pyridoxal phosphate (0.25 mmol/kg) protected against convulsions and death produced by low doses of MDTC or TCH, and low or high doses of TSC. Pretreatment with pyridoxine hydrochloride (0.25 mmol/kg) protected mice against TSC but not against TCH. It protected against low doses of MDTC (0.12 mmol/kg), but shortened the latency to convulsions after intermediate doses of MDTC (0.37 mmol/kg). Glutamate decarboxylase activity (GAD, EC 4.1.1.15) in whole brain homogenates from mice killed at the onset of seizures, was significantly reduced by all 3 drugs at all doses. This inhibition did not exceed 30% after any dose of TSC or TCH, but was 64% in mice killed 4 min after the injection of MDTC (0.98 mmol/kg). The addition of pyridoxal phosphate to brain homogenates abolished GAD inhibition after MDTC but not after TCH. In vitro brain GAD was 50% inhibited by 10−4m -MDTC, 18% by 10−4m -TSC and 8% by 10 −4m -TCH. Kinetic studies suggested that at low concentrations MDTC inhibits by competing with pyridoxal phosphate. At the onset of convulsions the cerebral content of pyridoxal phosphate was reduced after low or high doses of TSC (0.27 and 2.2 mmol/kg) and after high doses of MDTC (0.98 mmol/kg). All three drugs (at 10−5−10−4m ) inhibited pyridoxal phosphokinase (EC 2.7.1.35) in vitro. Short latency convulsions after MDTC (0.37–0.98 mmol/kg) very probably arise from inhibition of cerebral GAD, due to competition for coenzymic sites and/or unavailability of coenzyme. Long-latency convulsions after MDTC (0.12–0.37 mmol/kg) are comparable to those seen after TSC (0.27–2.2 mmol/kg) and may depend on a mechanism additional to inhibition of GAD. 相似文献
2.
Uxmal and Tulum are two important Mayan sites in the Yucatan peninsula. The buildings are mainly composed of limestone and grey/black discoloration is seen on exposed walls and copious greenish biofilms on inner walls. The principal microorganisms detected on interior walls at both Uxmal and Tulum were cyanobacteria; heterotrophic bacteria and filamentous fungi were also present. A dark‐pigmented mitosporic fungus and Bacillus cereus, both isolated from Uxmal, were shown to be acidogenic in laboratory cultures. Cyanobacteria belonging to rock‐degrading genera Synechocystis and Gloeocapsa were identified at both sites. Surface analysis previously showed that calcium ions were present in the biofilms on buildings at Uxmal and Tulum, suggesting the deposition of biosolubilized stone. Apart from their potential to degrade the substrate, the coccoid cyanobacteria supply organic nutrients for bacteria and fungi, which can produce organic acids, further increasing stone degradation. 相似文献
3.
4.
Deregulation of microRNAs by HIV-1 Vpr protein leads to the development of neurocognitive disorders.
5.
Novak V Yang AC Lepicovsky L Goldberger AL Lipsitz LA Peng CK 《Biomedical engineering online》2004,3(1):39
Background
This study evaluated the effects of stroke on regulation of cerebral blood flow in response to fluctuations in systemic blood pressure (BP). The autoregulatory dynamics are difficult to assess because of the nonstationarity and nonlinearity of the component signals.Methods
We studied 15 normotensive, 20 hypertensive and 15 minor stroke subjects (48.0 ± 1.3 years). BP and blood flow velocities (BFV) from middle cerebral arteries (MCA) were measured during the Valsalva maneuver (VM) using transcranial Doppler ultrasound.Results
A new technique, multimodal pressure-flow analysis (MMPF), was implemented to analyze these short, nonstationary signals. MMPF analysis decomposes complex BP and BFV signals into multiple empirical modes, representing their instantaneous frequency-amplitude modulation. The empirical mode corresponding to the VM BP profile was used to construct the continuous phase diagram and to identify the minimum and maximum values from the residual BP (BPR) and BFV (BFVR) signals. The BP-BFV phase shift was calculated as the difference between the phase corresponding to the BPR and BFVR minimum (maximum) values. BP-BFV phase shifts were significantly different between groups. In the normotensive group, the BFVR minimum and maximum preceded the BPR minimum and maximum, respectively, leading to large positive values of BP-BFV shifts.Conclusion
In the stroke and hypertensive groups, the resulting BP-BFV phase shift was significantly smaller compared to the normotensive group. A standard autoregulation index did not differentiate the groups. The MMPF method enables evaluation of autoregulatory dynamics based on instantaneous BP-BFV phase analysis. Regulation of BP-BFV dynamics is altered with hypertension and after stroke, rendering blood flow dependent on blood pressure.6.
Anderson DH Sawaya MR Cascio D Ernst W Modlin R Krensky A Eisenberg D 《Journal of molecular biology》2003,325(2):355-365
Our crystal structure of granulysin suggests a mechanism for lysis of bacterial membranes by granulysin, a 74-residue basic protein from human cytolytic T lymphocyte and natural killer cells. We determined the initial crystal structure of selenomethionyl granulysin by MAD phasing at 2A resolution. We present the structure model refined using native diffraction data to 0.96A resolution. The five-helical bundle of granulysin resembles other "saposin folds" (such as NK-lysin). Positive charges distribute in a ring around the granulysin molecule, and one face has net positive charge. Sulfate ions bind near the segment of the molecule identified as most membrane-lytic and of highest hydrophobic moment. The ion locations may indicate granulysin's orientation of initial approach towards the membrane. The crystal packing reveals one way to pack a sheet of granulysin molecules at the cell surface for a concerted lysis effort. The energy of binding granulysin charges to the bacterial membrane could drive the subsequent lytic processes. The loosely packed core facilitates a hinge or scissors motion towards exposure of hydrophobic surface that we propose tunnels the granulysin into the fracturing target membrane. 相似文献
7.
OBJECTIVE: To determine if cytologic screening is associated with early stage at diagnosis of and decreased mortality from invasive adenocarcinoma and adenosquamous carcinoma of the uterine cervix. STUDY DESIGN: We retrospectively reviewed the medical records of all 169 women diagnosed with invasive adenocarcinoma or adenosquamous carcinoma of the cervix in a prepaid health plan during 1988-1994. Differences in stage and survival were assessed in relation to screening history and symptoms. RESULTS: Among the 169 cases, late-stage disease was present in 19/169 women (11.2%) at the time of diagnosis, and 24/269 (14.2%) women died of the disease during the three-year follow-up period. Women whose cancer was screen detected numbered 48/169 (28.4%) and were less likely to present with late-stage disease than non-screen-detected women: 2/48 (4.2%) versus 17/121 (14.0%) (P = .05). A mortality advantage at three years from diagnosis was associated with screen-detected cancers: 1/48 (2.1%) versus 23/121 (19.0%) (P = .002), and this advantage persisted after controlling for stage at diagnosis. CONCLUSION: Invasive adenocarcinomas and adenosquamous carcinomas of the cervix detected by screening are found at an earlier stage and are associated with lower disease-specific mortality than those not detected by screening. 相似文献
8.
Crystal structure of a major secreted protein of Mycobacterium tuberculosis-MPT63 at 1.5-A resolution
下载免费PDF全文
![点击此处可从《Protein science : a publication of the Protein Society》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Goulding CW Parseghian A Sawaya MR Cascio D Apostol MI Gennaro ML Eisenberg D 《Protein science : a publication of the Protein Society》2002,11(12):2887-2893
MPT63 is a small, major secreted protein of unknown function from Mycobacterium tuberculosis that has been shown to have immunogenic properties and has been implicated in virulence. A BLAST search identified that MPT63 has homologs only in other mycobacteria, and is therefore mycobacteria specific. As MPT63 is a secreted protein, mycobacteria specific, and implicated in virulence, MPT63 is an attractive drug target against the deadliest infectious disease, tuberculosis (TB). As part of the TB Structural Genomics Consortium, the X-ray crystal structure of MPT63 was determined to 1.5-Angstrom resolution with the hope of yielding functional information about MPT63. The structure of MPT63 is an antiparallel beta-sandwich immunoglobulin-like fold, with the unusual feature of the first beta-strand of the protein forming a parallel addition to the small antiparallel beta-sheet. MPT63 has weak structural similarity to many proteins with immunoglobulin folds, in particular, Homo sapiens beta2-adaptin, bovine arrestin, and Yersinia pseudotuberculosis invasin. Although the structure of MPT63 gives no conclusive evidence to its function, structural similarity suggests that MPT63 could be involved in cell-host interactions to facilitate endocytosis/phagocytosis. 相似文献
9.
Within minutes after infecting Escherichia coli, bacteriophage T7 synthesizes many copies of its genomic DNA. The lynchpin of the T7 replication system is a bifunctional primase-helicase that unwinds duplex DNA at the replication fork while initiating the synthesis of Okazaki fragments on the lagging strand. We have determined a 3.45 A crystal structure of the T7 primase-helicase that shows an articulated arrangement of the primase and helicase sites. The crystallized primase-helicase is a heptamer with a crown-like shape, reflecting an intimate packing of helicase domains into a ring that is topped with loosely arrayed primase domains. This heptameric isoform can accommodate double-stranded DNA in its central channel, which nicely explains its recently described DNA remodeling activity. The double-jointed structure of the primase-helicase permits a free range of motion for the primase and helicase domains that suggests how the continuous unwinding of DNA at the replication fork can be periodically coupled to Okazaki fragment synthesis. 相似文献
10.
Danilo E Xavier Renata C Picão Raquel Girardello Lorena CC Fehlberg Ana C Gales 《BMC microbiology》2010,10(1):217