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51.
Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases 总被引:5,自引:2,他引:5
Huang JQ; Trasler JM; Igdoura S; Michaud J; Hanal N; Gravel RA 《Human molecular genetics》1997,6(11):1879-1885
Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative
diseases resulting from the inability to catabolize GM2 ganglioside by
beta-hexosaminidase A (Hex A) due to mutations of the alpha subunit
(Tay-Sachs disease) or beta subunit (Sandhoff disease) of Hex A. Hex B
(beta beta homodimer) is also defective in Sandhoff disease. We previously
developed mouse models of both diseases and showed that Hexa-/- (Tay-Sachs)
mice remain asymptomatic to at least 1 year of age while Hexb-/- (Sandhoff)
mice succumb to a profound neurodegenerative disease by 4-6 months of age.
Here we find that neuron death in Hexb-/- mice is associated with apoptosis
occurring throughout the CNS, while Hexa-/- mice were minimally involved at
the same age. Studies of autopsy samples of brain and spinal cord from
human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances,
in keeping with the severe expression of both diseases. We suggest that
neuron death is caused by unscheduled apoptosis, implicating accumulated
GM2 ganglioside or a derivative in triggering of the apoptotic cascade.
相似文献
52.
The bias favoring deletion over inversion in DH-JH rearrangement has been
known for years, but the underlying mechanism has yet to be fully defined.
It has been suggested that the ratio of deletion/inversion is determined by
the combined effect of two factors: (i) the relative strengths of 5' and 3'
recombination signal sequences (RSS) of a DH segment, and (ii) the
efficiency with which the deletional product (one joint) forms relative to
the inversional product (two joints). In this study, we analyzed for the
first time the effect of factor 1 alone on the biased 3' RSS utilization in
DH-JH joining by using deletional plasmids in an extrachromosomal substrate
V(D)J recombination assay. It was found that the 3' RSS and associated
coding end (12 bp) mediate recombination more efficiently than the 5'
RSS/coding end DH-JH plasmids. These results demonstrate that the effect of
the RSS/coding end alone can account, at least partially, for the
predominant deletion in DH-JH recombination. The potential effect of the
relative strength of RSS and associated coding end on the ordered
rearrangement of DH-JH followed by VH to DH-JH was also assessed. When
recombination frequencies of D-->J (3' DH to J3) were compared with
frequencies of V-- >D (VHPJ14 to 3' DH or VHOX2 to 3' DH), it was found
that V-->D joining was, if anything, more efficient than D-->J
joining. Therefore, if all three segments were accessible, RSS/coding end
effects would not contribute to the ordered rearrangement of the IgH locus.
相似文献
53.
JM Hopkin 《Current opinion in immunology》1997,9(6):788-792
Atopy — a T helper 2 cell driven hypersensitivity to innocuous antigens (allergens) which causes most cases of asthma — is of complex genetic and environmental origins. There is compelling epidemiological evidence for a rise in atopic disease in ‘westernised’ communities. The changing pattern of microbial exposure in early childhood is suggested to be the principal candidate mechanism for this rise. 相似文献
54.
The effects of an enhanced inflammatory reaction on the surface properties of cast Biomer 总被引:1,自引:0,他引:1
R E Marchant J M Anderson E Castillo A Hiltner 《Journal of biomedical materials research》1986,20(2):153-168
The ability of a biomaterial to withstand the rigors of the harsh biologic environment is an important consideration when considering a material for long-term biomedical applications. Using a cage implant system, the effects of an intense inflammatory reaction on cast Biomer have been investigated. The inflammatory response to cast Biomer was greatly increased by coimplanting Biomer films with a cytotoxic poly(vinyl chloride) (PVC) in rats for a period of 21 days. Cast Biomer films were characterized by weight, advancing contact angle with water in air, attenuated total reflectance infrared spectroscopy and scanning electron microscopy (SEM). The analyses were performed before any treatment, after autoclaving and sonication, and after 21 days implantation with the cytotoxic (PVC) in rats. The results of the study indicated that cast Biomer does not undergo significant chemical degradation when subjected to the effects of an intense inflammatory reaction for 21 days. Implantation does, however, lead to rearrangement that results in a more polar and hydrophilic surface, suggesting that the polymer adapts to the hydrophilic environment of the inflammatory exudate. 相似文献
55.
56.
The walls of the third ventricle have been proposed to serve as a bidirectional conduit for exchanges between the neural parenchyma and the cerebrospinal fluid. In immunohistochemical studies of mice, we observed that light exposure and circadian phase affected peptide staining surrounding the third ventricle at the level of the suprachiasmatic nuclei. Under high magnification, we observed robust staining for the neurohormone oxytocin and the calcium-binding protein parvalbumin associated with cilia extending into the third ventricle from the surrounding ventricular wall; no similar staining was observed for vasopressin or calbindin. Retinal illumination had opposite effects on levels of parvalbumin and oxytocin in the cilia: light exposure during late subjective night increased oxytocin staining, but decreased parvalbumin staining in the cilia. Preventing cellular transport with colchicine eliminated immunohistochemical staining for oxytocin in the cilia. There was also a significant daily rhythm of oxytocin immunostaining in the third ventricle wall, and in magnocellular neurons in the anterior hypothalamus. The results suggest that environmental lighting and circadian rhythms regulate levels of oxytocin in the cerebrospinal fluid, possibly by regulating movement of oxytocin through the third ventricle wall. 相似文献
57.
DL?MagerEmail author AD?Haffajee PM?Devlin CM?Norris MR?Posner JM?Goodson 《Journal of translational medicine》2005,3(1):27
Background
The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls. 相似文献58.
M O Péquignot A C Provost S Sallé P Taupin K M Sainton D Marchant J C Martinou J C Ameisen J-P Jais M Abitbol 《Developmental dynamics》2003,228(2):231-238
Apoptosis plays a major role in the development of the central nervous system. Previous studies of apoptosis induction during retinal development are difficult to interpret, however, because they explored different mouse strains, different developmental periods, and used different assays. Here, we first established a comprehensive sequential pattern of cell death during the whole development of the C57BL/6J mouse retina, from E10.5 to postnatal day (P) 21 by using the terminal deoxynucleotidyl transferase (TdT) -mediated deoxyuridine triphosphate (dUTP)-biotinylated nick end labeling (TUNEL) assay. We confirmed the existence of three previously described apoptotic peaks and identified another, later peak at P15, in both the outer nuclear layer, in which the photoreceptors differentiate, and the ganglion cell layer. Comparison of wild-type C57BL/6 mice, gld mice, defective in the death ligand fasL, and bax-/- mice, defective in the pro-apoptotic BAX protein, revealed a minor role for FAS ligand but a crucial role for BAX in both apoptosis and normal retinal development. The lack of BAX resulted in thicker than normal inner neuroblastic and ganglion cell layers in adults, with larger numbers of cells and an impaired electroretinogram response related to a decreased number of responsive cells. Our findings indicate that cell death during normal retinal development is important for the modeling of a functional vision organ and showed that the pro-apoptotic BAX protein plays a crucial role in this process. 相似文献
59.
Marchant D Gogat K Boutboul S Péquignot M Sternberg C Dureau P Roche O Uteza Y Hache JC Puech B Puech V Dumur V Mouillon M Munier FL Schorderet DF Marsac C Dufier JL Abitbol M 《Human mutation》2001,17(3):235
ABSTRACT We report five novel VMD2 mutations in Best's macular dystrophy patients (S16F, I73N, R92H, V235L, and N296S). An SSCP analysis of the VMD2 11 exons revealed electrophoretic mobility shifts exclusively in exons 2, 3, 4, 6 and 8. Direct sequencing indicated that these shifts are caused by mono-allelic transition in exons 2, 4, 6, 8 and transversion in exons 3 and 6. Five novel "silent" polymorphisms are also reported: 213T>C, 323C>A, 1514A>G, 1661C>T, and 1712T>C. Hum Mutat 17:235, 2001. 相似文献
60.
The effectiveness of a treatment protocol for male lower urinary tract symptoms in general practice: a practical randomised controlled trial 下载免费PDF全文
Roelf JC Norg Kees van de Beek Piet JM Portegijs CP Onno van Schayck J Andr Knottnerus 《The British journal of general practice》2006,56(533):938-944
BACKGROUND: Randomised controlled trials have shown the efficacy of several treatment modalities for lower urinary tract symptoms (LUTS) in selected populations. The effectiveness in daily practice has hardly been investigated, especially in primary care and is dependent on choices between all possible treatment options and best investigated in a comprehensive study, including all treatment modalities (watchful waiting, alpha-blockers, 5-alpha-reductase inhibitors, and surgery). AIM: Assessment of the effectiveness of a comprehensive treatment protocol for LUTS in primary care. DESIGN OF STUDY: Randomised controlled trial. SETTING: Fourteen general practices in the Netherlands. METHOD: Intervention: treatment protocol based on a formalised expert opinion. Control condition: usual care. Study population: 208 subjects with moderate to severe LUTS (IPSS > or =8, median = 13). OUTCOME MEASURES: symptom severity (IPSS [International Prostate Symptom Score]), bother score (Dan-PSS [Danish Prostate Symptom Score]), and maximum urinary flow (Q(max)); incidence of acute urinary retention and urinary tract infections. RESULTS: In the intervention group markedly more subjects used an alpha-blocker at end of follow-up than in the usual care group (24% versus 6%). No significant differences were found between intervention and control group in IPSS, Q(max) or Dan-PSS. CONCLUSION: alpha-blockers and watchful waiting are the most frequent treatment modalities for LUTS in primary care. Our study showed no evidence that a protocol using well-defined indications for all possible treatment modalities based on a formalised expert opinion procedure has added value. Based on our results, we cannot recommend a broadening of the indication for alpha-blockers, which, however, seems to be the current trend. 相似文献