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141.
Richard Lu Bobby Brooke Herrera Heather D. Eshleman Yang Fu Alexander Bloom Zhigang Li David B. Sacks Marcia B. Goldberg 《PLoS pathogens》2015,11(10)
The intracellular bacterial pathogen Shigella infects and spreads through the human intestinal epithelium. Effector proteins delivered by Shigella into cells promote infection by modulating diverse host functions. We demonstrate that the effector protein OspB interacts directly with the scaffolding protein IQGAP1, and that the absence of either OspB or IQGAP1 during infection leads to larger areas of S. flexneri spread through cell monolayers. We show that the effect on the area of bacterial spread is due to OspB triggering increased cell proliferation at the periphery of infected foci, thereby replacing some of the cells that die within infected foci and restricting the area of bacterial spread. We demonstrate that OspB enhancement of cell proliferation results from activation of mTORC1, a master regulator of cell growth, and is blocked by the mTORC1-specific inhibitor rapamycin. OspB activation of mTORC1, and its effects on cell proliferation and bacterial spread, depends on IQGAP1. Our results identify OspB as a regulator of mTORC1 and mTORC1-dependent cell proliferation early during S. flexneri infection and establish a role for IQGAP1 in mTORC1 signaling. They also raise the possibility that IQGAP1 serves as a scaffold for the assembly of an OspB-mTORC1 signaling complex. 相似文献
142.
Sara A. DiVall Danny Herrera Bonnie Sklar Sheng Wu Fredric Wondisford Sally Radovick Andrew Wolfe 《PloS one》2015,10(3)
Infertility associated with obesity is characterized by abnormal hormone release from reproductive tissues in the hypothalamus, pituitary, and ovary. These tissues maintain insulin sensitivity upon peripheral insulin resistance. Insulin receptor signaling may play a role in the dysregulation of gonadotropin-releasing hormone (GnRH) secretion in obesity, but the interdependence of hormone secretion in the reproductive axis and the multi-hormone and tissue dysfunction in obesity hinders investigations of putative contributing factors to the disrupted GnRH secretion. To determine the role of GnRH insulin receptor signaling in the dysregulation of GnRH secretion in obesity, we created murine models of diet-induced obesity (DIO) with and without intact insulin signaling in the GnRH neuron. Obese control female mice were infertile with higher luteinizing hormone levels and higher GnRH pulse amplitude and total pulsatile secretion compared to lean control mice. In contrast, DIO mice with a GnRH specific knockout of insulin receptor had improved fertility, luteinizing hormone levels approaching lean mice, and GnRH pulse amplitude and total secretion similar to lean mice. Pituitary responsiveness was similar between genotypes. These results suggest that in the obese state, insulin receptor signaling in GnRH neurons increases GnRH pulsatile secretion and consequent LH secretion, contributing to reproductive dysfunction. 相似文献
143.
144.
André R. A. Marques Jan Aten Roelof Ottenhoff Cindy P. A. A. van Roomen Daniela Herrera Moro Nike Claessen María Fernanda Vinueza Veloz Kuikui Zhou Zhanmin Lin Mina Mirzaian Rolf G. Boot Chris I. De Zeeuw Herman S. Overkleeft Yildiz Yildiz Johannes M. F. G. Aerts 《PloS one》2015,10(8)
The enzyme glucocerebrosidase (GBA) hydrolyses glucosylceramide (GlcCer) in lysosomes. Markedly reduced GBA activity is associated with severe manifestations of Gaucher disease including neurological involvement. Mutations in the GBA gene have recently also been identified as major genetic risk factor for Parkinsonism. Disturbed metabolism of GlcCer may therefore play a role in neuropathology. Besides lysosomal GBA, cells also contain a non-lysosomal glucosylceramidase (GBA2). Given that the two β-glucosidases share substrates, we speculated that over-activity of GBA2 during severe GBA impairment might influence neuropathology. This hypothesis was studied in Niemann-Pick type C (Npc1
-/-) mice showing secondary deficiency in GBA in various tissues. Here we report that GBA2 activity is indeed increased in the brain of Npc1
-/- mice. We found that GBA2 is particularly abundant in Purkinje cells (PCs), one of the most affected neuronal populations in NPC disease. Inhibiting GBA2 in Npc1
-/- mice with a brain-permeable low nanomolar inhibitor significantly improved motor coordination and extended lifespan in the absence of correction in cholesterol and ganglioside abnormalities. This trend was recapitulated, although not to full extent, by introducing a genetic loss of GBA2 in Npc1
-/- mice. Our findings point to GBA2 activity as therapeutic target in NPC. 相似文献
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147.
In the terrestrial bromeliad, Puya floccosa, a value of carbon isotopic composition (δ13C) of −22‰ has been previously reported, suggesting the operation of weak and/or intermediate (C3-CAM) crassulacean acid metabolism (CAM). In order to characterize the operation of CAM in P. floccosa and its possible induction by drought, plants were grown in Caracas and subjected to four independent drought cycles. Additionally,
since plants of this species grow in Venezuela in a large range of elevations, leaf samples were collected at elevations ranging
from 725 to 2,100 m a.s.l. in the Venezuelan Andes and the Coastal Range, in order to evaluate the effect of elevation on
CAM performance. Even though nocturnal acid accumulation occurred in both watered and droughted plants, mean ΔH+ was higher in droughted than watered plants [ΔH+ = 60.17.5 and 22.9 ± 5.2 μmol g−1(FM), respectively]. The majority of plants from all the natural populations sampled had low values of δ13C not differing significantly from those of C3 plants collected as standards and δ13C did not change with elevation. We conclude that P. floccosa is capable of a weak CAM activity, with a large variability among populations and drought experiments probably due to local
and temporal differences in microclimatic variables and drought stress; elevation bears no influence on values of δ13C in this species. 相似文献
148.
Ricardo Estrada María Herrera lvaro Segura Javier Araya Carlos Boschini Jos María Gutirrez Guillermo Len 《Biologicals》2010,38(6):664-669
Administration of antivenoms to treat snakebite envenomings has the potential risk of inducing early adverse reactions. The mechanisms involved in these reactions are unclear. In this study, polyspecific antivenom consisting of whole IgG purified from equine plasma by caprylic acid precipitation was administered intravenously to non-envenomed horses (n = 47) and cows (n = 20) at a dose of 0.4 mL/kg. It has been reported that, in humans, this formulation (administered at a dose of 0.4 mL/kg) induces mild noticeable early adverse reactions, such as fever, vomiting, diarrhea, urticaria, generalized rash, tachypnea or tachycardia, in about 15–20% of the patients. Unexpectedly, none of the animals receiving antivenom in our study showed any evidence of early adverse reaction. Moreover, no late adverse reactions, i.e. serum sickness, were observed during 40 days after antivenom administration. Unlike studies performed in envenomed humans, our present results were obtained in a group of non-envenomed individuals. It is concluded that, in addition to the physicochemical characteristics of the formulation, other unknown factors must determine the occurrence of adverse reactions in snakebite envenomed humans treated with equine-derived antivenoms. 相似文献
149.
Marcelino Herrera Ismael Hachero-Cruzado Alicia Naranjo Juan Miguel Mancera 《Reviews in Fish Biology and Fisheries》2010,20(4):489-497
In this work, several features during the wedge sole larval development have been described. The newly hatched larva presented
an acidophilic yolk with some oil drops. The digestive tract began to differentiate at 1 DAH, with a loop being discernible.
The pancreas and liver were completely formed at 2 DAH, the former showing its typical basophilic acinar structure and acidophilic
zymogen granules. The first supranuclear vesicles in enterocytes were seen at 3 DAH. At 4 DAH, yolk reserves were completely
exhausted, the number of oesophagus and intestine mucous cells increased, and the heart was differentiated into four chambers:
the venous sinus, atrium, ventricle, and arterious bulb. The development was fast and almost all organs were differentiated
at 2 DAH. It is important to emphasize that gastric glands were not detected, a factor that should be considered when deciding
diet formulation and feeding strategies for the rearing of this species. 相似文献
150.
Zacariah L. Hildenbrand Sudheer K. Molugu Atanu Paul Gustavo A. Avila Nadia Herrera Chuan Xiao Marc B. Cox Ricardo A. Bernal 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(28):2760-2764
Hsp90 is a ubiquitous molecular chaperone that plays a key role in the malignant development of hormone-dependent pathologies such as cancer. An important role for Hsp90 is to facilitate the stable binding of steroid hormones to their respective receptors enabling the ligand-based signal to be carried to the nucleus and ultimately resulting in the up-regulation of gene expression. Along with Hsp90, this dynamic and transient process also involves the recruitment of additional proteins and co-chaperones that add further stability to the mature receptor–chaperone complex. In the work presented here, we describe four new protocols for the bacterial over-expression and column chromatographic purification of the human p23, FKBP52, HOP and SGTα proteins. Each of these proteins plays a distinct role in the steroid hormone receptor regulatory cycle. Affinity, ion-exchange and size-exclusion techniques were used to produce target yields greater than 50 mg/L of cultured media, with each purified sample reaching near absolute sample homogeneity. These results reveal a reliable system for the production of p23, FKBP52, HOP and SGTα substrate proteins for use in the investigation of the Hsp90-associated protein interactions of the steroid hormone receptor cycle. 相似文献