全文获取类型
收费全文 | 590篇 |
免费 | 34篇 |
专业分类
624篇 |
出版年
2023年 | 4篇 |
2022年 | 3篇 |
2021年 | 6篇 |
2020年 | 3篇 |
2019年 | 10篇 |
2018年 | 14篇 |
2017年 | 5篇 |
2016年 | 16篇 |
2015年 | 24篇 |
2014年 | 25篇 |
2013年 | 47篇 |
2012年 | 36篇 |
2011年 | 54篇 |
2010年 | 31篇 |
2009年 | 24篇 |
2008年 | 25篇 |
2007年 | 32篇 |
2006年 | 30篇 |
2005年 | 34篇 |
2004年 | 39篇 |
2003年 | 20篇 |
2002年 | 25篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 10篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1991年 | 4篇 |
1989年 | 2篇 |
1988年 | 5篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1984年 | 8篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 6篇 |
1980年 | 4篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1974年 | 4篇 |
1973年 | 5篇 |
1972年 | 2篇 |
1933年 | 2篇 |
1897年 | 2篇 |
排序方式: 共有624条查询结果,搜索用时 0 毫秒
561.
Diano N Grano V Rossi S Bencivenga U Portaccio M Amato U Carfora F Lepore M Gaeta FS Mita DG 《Biotechnology progress》2004,20(2):457-466
A hollow-fiber enzyme reactor, operating under isothermal and nonisothermal conditions, was built employing a polypropylene hollow fiber onto which beta-galactosidase was immobilized. Hexamethylenediamine and glutaraldehyde were used as spacer and coupling agent, respectively. Glucose production was studied as a function of temperature, substrate concentration, and size of the transmembrane temperature gradient. The actual average temperature differences across the polypropylene fiber, to which reference was done to evaluate the effect of the nonisothermal conditions, were calculated by means of a mathematical approach, which made it possible to know, using computer simulation, the radial and axial temperature profiles inside the bioreactor and across the membrane. Percent activity increases, proportional to the size of the temperature gradients, were found when the enzyme activities under nonisothermal conditions were compared to those measured under comparable isothermal conditions. Percent reductions of the production times, proportional to the applied temperature gradients, were also calculated. The advantage of employing nonisothermal bioreactors in biotechnological industrial process was discussed. 相似文献
562.
563.
A sequence homologous to an internal fragment 0.75 kb BstXI of the Pseudomonas syringae pv. syringae hrpZ gene was identified in Pseudomonas syringae pv. aptata NCPPB 2664, the causal agent of bacterial blight in sugar beet, lettuce and other plants, and in E. coli DH10B (pCCP1069) containing the P. syringae pv. aptata hrp gene cluster. PCR with oligonucleotides, based on the hrpZPss gene and used as primers with the total genomic DNA of P. syringae pv. aptata, amplified a 1 kb fragment that hybridized with the probe in highly stringent conditions. The amplicon was cloned into the pGEM-T® plasmid vector, amplified in E. coli DH5 and sequenced. The sequence showed 95%, 83% and 61% identity with those of hrpZPss, hrpZPsg and hrpZPst genes encoding the harpins of the P. syringae pv. syringae, glycinea and tomato, respectively. The amplicon was cloned into the pMAL® expression system. The expressed protein, fused with maltose-binding protein, was cleaved with a specific protease factor Xa, and purified using affinity chromatography. On the basis of the amino acid sequence and its ability to induce HR in tobacco leaves, it was identified as a P. syringae pv. aptata harpin. 相似文献
564.
565.
A Bearz R Talamini G Rossoni A Santo V de Pangher G Fasola F Rosetti A Favaretto V Gregorc M Berretta S Santarossa E Berto U Tirelli 《BMC research notes》2012,5(1):482
ABSTRACT: BACKGROUND: Although first-line therapy for patients affected by advanced mesothelioma is well established, there is a lack of data regarding the impact of second-line treatment. METHODS: We retrospectively collected data of patients affected by advanced mesothelioma, already treated with first-line therapy based on pemetrexed and platin, with a response (partial response or stable disease) lasting at least 6 months, and re-treated with a pemetrexed-based therapy at progression. The primary objective was to describe time to progression and overall survival after re-treatment. RESULTS: Overall across several Italian oncological Institutions we found 30 patients affected by advanced mesothelioma, in progression after a 6-month lasting clinical benefit following a first-line treatment with cisplatin and pemetrexed, and re-challenged with a pemetrexed-based therapy. In these patients we found a disease control rate of 66%, with reduction of pain in 43% of patients. Overall time to progression and survival were promising for a second-line setting of patients with advanced mesothelioma, being 5.1 and 13.6 months, respectively. CONCLUSIONS: In our opinion, when a patient experience a long-lasting benefit from previous treatment with pemetrexed combined with a platin compound, the same treatment should be offered at progression. 相似文献
566.
Low concentrations of isothiocyanates protect mesenchymal stem cells from oxidative injuries, while high concentrations exacerbate DNA damage 总被引:1,自引:0,他引:1
Zanichelli F Capasso S Di Bernardo G Cipollaro M Pagnotta E Cartenì M Casale F Iori R Giordano A Galderisi U 《Apoptosis : an international journal on programmed cell death》2012,17(9):964-974
Isothiocyanates (ITCs) are molecules naturally present in many cruciferous vegetables (broccoli, black radish, daikon radish, and cauliflowers). Several studies suggest that cruciferous vegetable consumption may reduce cancer risk and slow the aging process. To investigate the effect of ITCs on cellular DNA damage, we evaluated the effects of two different ITCs [sulforaphane (SFN) and raphasatin (RPS)] on the biology of human mesenchymal stem cells (MSCs), which, in addition to their ability to differentiate into mesenchymal tissues, contribute to the homeostatic maintenance of many organs. The choice of SFN and RPS relies on two considerations: they are among the most popular cruciferous vegetables in the diet of western and eastern countries, respectively, and their bioactive properties may differ since they possess specific molecular moiety. Our investigation evidenced that MSCs incubated with low doses of SFN and RPS show reduced in vitro oxidative stress. Moreover, these cells are protected from oxidative damages induced by hydrogen peroxide, while no protection was evident following treatment with the UV ray of a double strand DNA damaging drug, such as doxorubicin. High concentrations of both ITCs induced cytotoxic effects in MSC cultures and further increased DNA damage induced by peroxides. In summary, our study suggests that ITCs, at low doses, may contribute to slowing the aging process related to oxidative DNA damage. Moreover, in cancer treatment, low doses of ITCs may be used as an adjuvant to reduce chemotherapy-induced oxidative stress, while high doses may synergize with anticancer drugs to promote cell DNA damage. 相似文献
567.
Squillaro T Alessio N Cipollaro M Melone MA Hayek G Renieri A Giordano A Galderisi U 《Molecular biology of the cell》2012,23(8):1435-1445
MECP2 protein binds preferentially to methylated CpGs and regulates gene expression by causing changes in chromatin structure. The mechanism by which impaired MECP2 activity can induce pathological abnormalities in the nervous system of patients with Rett syndrome (RTT) is not clearly understood. To gain further insight into the role of MECP2 in human neurogenesis, we compared the neural differentiation process in mesenchymal stem cells (MSCs) obtained from a RTT patient and from healthy donors. We further analyzed neural differentiation in a human neuroblastoma cell line carrying a partially silenced MECP2 gene. Senescence and reduced expression of neural markers were observed in proliferating and differentiating MSCs from the RTT patient, which suggests that impaired activity of MECP2 protein may impair neural differentiation, as observed in RTT patients. Next, we used an inducible expression system to silence MECP2 in neuroblastoma cells before and after the induction of neural differentiation via retinoic acid treatment. This approach was used to test whether MECP2 inactivation affected the cell fate of neural progenitors and/or neuronal differentiation and maintenance. Overall, our data suggest that neural cell fate and neuronal maintenance may be perturbed by senescence triggered by impaired MECP2 activity either before or after neural differentiation. 相似文献
568.
569.
Fasciglione GF Gioia M Tsukada H Liang J Iundusi R Tarantino U Coletta M Pourmotabbed T Marini S 《Journal of biological inorganic chemistry》2012,17(4):663-672
The role of the hinge region in the unwinding and cleavage of type I collagen by interstitial collagenase (MMP-1) has been
studied at 37 °C and pH 7.3. The collagenolytic processing by MMP-1 displays a very similar overall rate for both chains of
collagen I, even though the affinity is higher for the α-1 chain and the cleavage rate is faster for the α-2 chain. MMP-1
binding to collagen I brings about a significant unwinding of the triple-helical arrangement only after the first cleavage
step of the α-1 and α-2 chains. The proteolytic processing by wild-type MMP-1 on a synthetic substrate and collagen I has
been compared with that observed for site-directed mutants obtained either by truncating the hinge region (∆255–272) or by
individually replacing the conserved amino acids Val268, Gly272, and Lys277 of the hinge region with residues observed for
the corresponding position in stromelysin-1 (MMP-3), a noncollagenolytic metalloproteinase. The ∆256–272 mutant has no collagenolytic
activity, clearly demonstrating the crucial role of this region for the enzymatic processing of collagen I. However, among
various mutants investigated, only Gly272Asp shows a dramatically reduced enzymatic activity both on the synthetic substrate
and on collagen I. This effect, however, is clearly related to the substituting residue, since substitution of Ala or Asn
for Gly272 does not have any effect on the kinetic properties of MMP-1. These data suggest that the substrate specificity
of MMP-1 is dictated by the reciprocal structural relationships between the catalytic domain and the carboxy-terminal domain
through the conformational arrangement of the hinge region. 相似文献
570.
The achievement of novel findings in stem cell research were the subject of the meeting organized by Stem Cell Research Italy (SCR Italy) and by the International Society for Cellular Therapy-Europe (ISCT). Stem cell therapy represents great promise for the future of molecular and regenerative medicine. The use of several types of stem cells is a real opportunity to provide a valid approach to curing several untreatable human diseases. Before it is suitable for clinical applications, stem cell biology needs to be investigated further and in greater detail. Basic stem cell research could provide exact knowledge regarding stem cell action mechanisms, and pre-clinical research on stem cells on an in vivo model of disease provides scientific evidence for future human applications. Applied stem cell research is a promising new approach to handling several diseases. Along with tissue engineering, it offers a new and promising discipline that can help to manage human pathologies through stem cell therapy. All of these themes were discussed in this meeting, covering stem cell subtypes with their newest basic and applied research. 相似文献