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201.
Dana Morrone Luke Lowry Mara K. Determan David M. Hershey Meimei Xu Reuben J. Peters 《Applied microbiology and biotechnology》2010,85(6):1893-1906
Engineering biosynthetic pathways in heterologous microbial host organisms offers an elegant approach to pathway elucidation
via the incorporation of putative biosynthetic enzymes and characterization of resulting novel metabolites. Our previous work
in Escherichia coli demonstrated the feasibility of a facile modular approach to engineering the production of labdane-related diterpene (20
carbon) natural products. However, yield was limited (<0.1 mg/L), presumably due to reliance on endogenous production of the
isoprenoid precursors dimethylallyl diphosphate and isopentenyl diphosphate. Here, we report incorporation of either a heterologous
mevalonate pathway (MEV) or enhancement of the endogenous methyl erythritol phosphate pathway (MEP) with our modular metabolic
engineering system. With MEP pathway enhancement, it was found that pyruvate supplementation of rich media and simultaneous
overexpression of three genes (idi, dxs, and dxr) resulted in the greatest increase in diterpene yield, indicating distributed metabolic control within this pathway. Incorporation
of a heterologous MEV pathway in bioreactor grown cultures resulted in significantly higher yields than MEP pathway enhancement.
We have established suitable growth conditions for diterpene production levels ranging from 10 to >100 mg/L of E. coli culture. These amounts are sufficient for nuclear magnetic resonance analyses, enabling characterization of enzymatic products
and hence, pathway elucidation. Furthermore, these results represent an up to >1,000-fold improvement in diterpene production
from our facile, modular platform, with MEP pathway enhancement offering a cost effective alternative with reasonable yield.
Finally, we reiterate here that this modular approach is expandable and should be easily adaptable to the production of any
terpenoid natural product. 相似文献
202.
203.
Kajsa Sjöholm Björn Carlsson Lena MS Carlsson 《Central European Journal of Biology》2006,1(2):221-234
The leptin system regulates body fat mass through a feedback loop between adipose tissue and the hypothalamus. To test if
leptin responsiveness may be regulated we assayed hypothalamic response to leptin during the estrous cycle; when changes in
food intake are known to occur. Immature rats were treated with pregnant mare’s serum gonadotropin (PMSG) to induce synchronized
follicular development, ovulation and corpus luteum formation. Leptin response was estimated by measuring the in vitro induction of tis11, a primary response gene activated by STAT3-dependent cytokines in hypothalamic explants after leptin stimulation. In addition,
mRNA levels of the suppressor cytokine signaling-3 (SOCS-3), a possible mediator of leptin resistance, were analyzed. Serum
leptin levels did not change between days 2 and day 3 (corresponding to proestrus and estrus, respectively) but the response
to leptin was higher on day 2 than on day 3 (p=0.05). Food intake displayed a tendency towards downregulation between day
1 and day 2 (p=0.057), and a tendency towards upregulation between day 2 and day 3 (p=0.072), although the body weight increased
on day of the study (p<0.0001). There was no significant difference in hypothalamic expression of SOCS-3 between day 2 and
day 3. In conclusion, we have shown that leptin responsiveness changes during a hormonally induced estrous cycle in rats.
Our data suggest that a change in the hypothalamic response to leptin may cause the cyclic feeding behavior seen in rats. 相似文献
204.
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206.
Gotsman M Dusa C Nassar H Hasin Y Lotan C Rozenman Y 《International journal of cardiovascular interventions》1999,2(3):187-190
The Cutting Balloon consists of a standard balloon dilatation catheter with four microtome-sharp blades that incise the plaque and minimize arterial wall trauma. It was used in 31 patients; nine had calcified arteries, ten had non-compliant lesions, three had in-stent restenosis and nine had aorto-ostial lesions. Seventeen lesions were predilated, 28 were post-dilated and 18 required stent implantation. The procedure was very effective in aorto-ostial lesions, non-compliant lesions that were not responsive to high-pressure balloon dilatation, and was partially successful in calcified arteries. It has a very specific niche in selected lesions. 相似文献
207.
208.
Love CC Thompson JA Brinsko SP Rigby SL Blanchard TL Lowry VK Varner DD 《Theriogenology》2003,60(6):1127-1138
Relationships between sperm motility parameters and viability were evaluated using two fluorescent staining techniques in fresh extended semen (fresh and after 24 h storage at 5 degrees C) that had various concentrations of dead sperm added to simulate different levels of viable and nonviable sperm. Both protocols incorporated SYBR-14 and propidium iodide (PI) while the second protocol added the mitochondrial probe JC-1. The relationship between total sperm motility and percent viable sperm was high between staining protocols (r = 0.98). Time (0 h versus 24 h, P<0.0001) and treatment (0, 10, 25, 50, and 75% nonviable sperm, P<0.0001) affected percent total sperm motility and percent viable sperm for both staining protocols. Actual percent viable sperm for each time and treatment did not differ from expected values. 相似文献
209.
Abkevich V Camp NJ Hensel CH Neff CD Russell DL Hughes DC Plenk AM Lowry MR Richards RL Carter C Frech GC Stone S Rowe K Chau CA Cortado K Hunt A Luce K O'Neil G Poarch J Potter J Poulsen GH Saxton H Bernat-Sestak M Thompson V Gutin A Skolnick MH Shattuck D Cannon-Albright L 《American journal of human genetics》2003,73(6):1271-1281
Major depression disorder is a common psychiatric disease with a major economic impact on society. In many cases, no effective treatment is available. The etiology of major depression is complex, but it is clear that the disease is, to a large extent, determined genetically, especially among individuals with a familial history of major depression, presumably through the involvement of multiple predisposition genes in addition to an environmental component. As a first step toward identification of chromosomal loci contributing to genetic predisposition to major depression, we have conducted a genomewide scan by using 628 microsatellite markers on 1,890 individuals from 110 Utah pedigrees with a strong family history of major depression. We identified significant linkage to major depression in males at marker D12S1300 (multipoint heterogeneity LOD score 4.6; P=.00003 after adjustment for multiple testing). With additional markers, the linkage evidence became highly significant, with the multipoint heterogeneity LOD score at marker D12S1706 increasing to 6.1 (P=.0000007 after adjustment for multiple testing). This study confirms the presence of one or more genes involved in psychiatric diseases on the q arm of chromosome 12 and provides strong evidence for the existence of a sex-specific predisposition gene to major depression at 12q22-q23.2. 相似文献
210.
Lucotte GL;French MS Consortium 《Genetic counseling (Geneva, Switzerland)》2002,13(2):133-138
To identify the chromosomal localizations of the multiple sclerosis (MS) genes, we conducted a genomewide linkage analysis using eighteen affected families. A MS gene is linked to markers located in the 19q13.3 region (multipoint lod-score = 2.1). Apolipoprotein E (ApoE) gene, located in this region, is an excellent candidate gene for MS because the ApoEe4 allele is acting as a severity allele in the disease. 相似文献