全文获取类型
收费全文 | 2756篇 |
免费 | 288篇 |
国内免费 | 17篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 162篇 |
妇产科学 | 64篇 |
基础医学 | 277篇 |
口腔科学 | 41篇 |
临床医学 | 234篇 |
内科学 | 601篇 |
皮肤病学 | 65篇 |
神经病学 | 144篇 |
特种医学 | 213篇 |
外科学 | 405篇 |
综合类 | 162篇 |
预防医学 | 185篇 |
眼科学 | 76篇 |
药学 | 133篇 |
中国医学 | 39篇 |
肿瘤学 | 256篇 |
出版年
2021年 | 41篇 |
2020年 | 31篇 |
2019年 | 31篇 |
2018年 | 38篇 |
2017年 | 30篇 |
2016年 | 31篇 |
2015年 | 40篇 |
2014年 | 86篇 |
2013年 | 64篇 |
2012年 | 105篇 |
2011年 | 95篇 |
2010年 | 110篇 |
2009年 | 85篇 |
2008年 | 88篇 |
2007年 | 93篇 |
2006年 | 101篇 |
2005年 | 119篇 |
2004年 | 76篇 |
2003年 | 86篇 |
2002年 | 65篇 |
2001年 | 74篇 |
2000年 | 81篇 |
1999年 | 66篇 |
1998年 | 71篇 |
1997年 | 80篇 |
1996年 | 70篇 |
1995年 | 48篇 |
1994年 | 41篇 |
1993年 | 47篇 |
1992年 | 62篇 |
1991年 | 53篇 |
1990年 | 72篇 |
1989年 | 79篇 |
1988年 | 77篇 |
1987年 | 73篇 |
1986年 | 52篇 |
1985年 | 59篇 |
1984年 | 49篇 |
1983年 | 40篇 |
1982年 | 34篇 |
1981年 | 22篇 |
1980年 | 26篇 |
1979年 | 32篇 |
1977年 | 24篇 |
1976年 | 27篇 |
1975年 | 23篇 |
1974年 | 22篇 |
1973年 | 31篇 |
1971年 | 27篇 |
1969年 | 20篇 |
排序方式: 共有3061条查询结果,搜索用时 15 毫秒
991.
992.
Lymphokine-activated killer cell functions in patients with leukemic B- lymphoproliferative diseases
van der Harst D; Brand A; van Luxemburg-Heys SA; Kooy-Winkelaar EM; van Rood JJ 《Blood》1989,74(7):2464-2470
Nine patients with leukemic B-lymphoproliferative diseases (B-LPD) were evaluated for development of in vitro recombinant interleukin-2 (rIL-2)- activated killer (LAK) cells. B-cell cultures were established from peripheral blood mononuclear cells (PBMNCs) containing 63% +/- 29% malignant cells. Short-term cultures were tested after 5-day activation with 500 U rIL-2/mL. Long-term cultures were maintained for 4 to 6 weeks by weekly addition of 500 U rIL-2 and autologous irradiated feeder cells. In the first week, the cells decreased considerably in the long-term cultures but thereafter cells proliferated (mainly T cells) on the average 300-fold (range 30- to 1,000-fold). In the short- term cultures, there was a 36% reduction of malignant B cells. In long- term cultures, B cells were reduced from 63% to 8%; three cultures still contained greater than 15% B cells. The CD16-positive cell percentage was comparable in both types of cultures and ranged from 2% to 17%. Effector cells lysing the natural killer (NK)-sensitive cell line K562 could be induced in all patients. Except in patients with chronic lymphocytic leukemia (CLL) and high malignant cell numbers, NK activity was already restored after 5 days. Optimal NK activity was obtained after 1.5 to 2.5 weeks. LAK cells killing NK-resistant lymphoma cell lines showed optimal activity after 2 to 3 weeks of culture. However, LAK cells killing greater than 10% of autologous malignant cells were obtained in only one third of the patients. The discrepancy between strong cytolytic activity against the NK-sensitive (K562) target cells obtained in all patients and the cytotoxic activity against NK-resistant cell lines contrasts with the poor development of LAK cells against autologous tumor cells. This discrepancy does not appear to be explained by soluble inhibitory factors released during the tumor cultures, as allogeneic LAK cells were not inhibited by supernatants from patients' cultures. Further investigations are warranted to reveal cell-mediated inhibition by tumor cells or suppressor cells. 相似文献
993.
Yarden N Lavelin I Genina O Hurwitz S Diaz R Brown EM Pines M 《General and comparative endocrinology》2000,117(2):173-181
Calcium-sensing receptor (CaR) gene expression and parathyroid hormone (PTH) content were evaluated in situ in chicken parathyroid glands (PG) in relation to changes in plasma calcium. The CaR gene is expressed by the parathyroid chief cells, the same cells that store and secrete PTH. An increase in plasma calcium, achieved by repletion of vitamin D-deficient chicks with a normal diet, by PTH injection, or during eggshell formation, increased the expression of the CaR gene. Low plasma calcium concentration in vitamin D-deficient chicks or in layers, before or after eggshell formation, was associated with decrease in CaR gene expression in the PG. The level of CaR gene expression was inversely correlated with the PTH content of the PG. The results of this study demonstrate for the first time that, in contrast to mammals, the CaR gene expression in the PG of the chicken is inversely associated with changes in plasma calcium. 相似文献
994.
Which clinical subgroups within the spectrum of child asthma are attributable to atopy? 总被引:6,自引:0,他引:6
Anne-Louise Ponsonby Paul Gatenby Nicholas Glasgow Raymond Mullins Tim McDonald Mark Hurwitz 《Chest》2002,121(1):135-142
STUDY OBJECTIVES: The contribution of atopy to childhood asthma has been debated. We aimed to examine the relationship between atopy and asthma, taking into account differences in respiratory symptoms and disease severity. DESIGN: A cross-sectional asthma survey involving the following: (1) a population sample of 758 (81% of eligible) school children aged 8 to 10 years from randomly selected schools in the Australian Capital Territory in 1999, and (2) a hospital-based sample of 78 (70% of eligible) children attending the hospital for asthma. Skin-prick test results to 10 common aeroallergens were available on 722 children and 77 children, respectively. Baseline spirometry was obtained on a subset of school children (n = 515, 78% of eligible). RESULTS: The association between atopy and wheeze by wheeze frequency over the past year was as follows: no episodes (odds ratio [OR], 1.00 [reference]), 1 to 3 episodes (OR, 3.27; 95% confidence interval [CI], 2.15 to 4.97), 4 to 12 episodes (OR, 3.44; 95% CI, 1.75 to 6.75), and > 12 episodes (OR, 8.70; 95% CI, 3.07 to 24.55), with a higher population attributable fraction (PAF) for > 12 episodes (75%) than 1 to 3 episodes (49%). Atopy was moderately related to asthma ever (OR, 2.09; 95% CI, 1.52 to 2.85; PAF, 33%) but strongly related to 1999 hospital attendance for asthma (OR, 16.95; 95% CI, 6.76 to 42.48; PAF, 89%). Adjustment for child age, gas heater use, and maternal smoking near the child did not materially alter these findings. CONCLUSIONS: The clinical features of frequent wheeze or hospital asthma attendance are largely attributable to atopy, but infrequent wheeze or a history of asthma ever are not. Atopic children are overrepresented in the severe range of the asthma spectrum. 相似文献
995.
E Kokia A Hurwitz E Ricciarelli C Tedeschi C E Resnick M D Mitchell E Y Adashi 《Endocrinology》1992,130(5):3095-3097
An increasing body of information now suggests the existence of a complete intraovarian IL-1 system replete with ligands, receptor, and receptor antagonist. Since IL-1 is an established mediator of inflammation and since ovulation may constitute an inflammatory-like reaction, consideration may be given to the possibility that IL-1 may play an intermediary role in the ovulatory process. To further assess the above hypothesis, we have set out to determine whether IL-1 is capable of promoting ovarian prostaglandin biosynthesis, an established component of the ovulatory cascade. Cultured whole ovarian dispersates from immature (25 day old) rats constitutively elaborated major prostaglandin species (PGE2 greater than PGF2 alpha) in a cell density-dependent fashion. Treatment with IL-1 produced dose-dependent increments in prostaglandin (PGE2 greater than PGF2 alpha) accumulation as compared with untreated controls. Comparable cellular densities of untreated or IL-1 beta-treated whole ovarian dispersates elaborated substantially more PGE2 as compared with isolated granulosa or theca-interstitial cell preparations suggesting a requirement for cell-cell interaction. Indeed, cell contact-dependent reconstitution experiments involving isolated granulosa and theca-interstitial cells at a projected physiologic ratio of 4:1 revealed synergistic interactions in the elaboration of PGE2 under both basal and IL-1 beta-treated circumstances. Identical results were obtained for cell contact-independent heterologous (but not homologous) coculture experiments. Taken together, our present findings reveal optimal basal and IL-1-stimulated ovarian prostaglandin (PGE2 greater than PGF2 alpha) biosynthesis to require heterologous, contact-independent, presumably humorally-mediated, cell-cell interaction. These observations along with the demonstration of the gonadotropin-dependent preovulatory induction of ovarian IL-1 beta gene expression provide strong support for the view that IL-1 may be the centerpiece of an intraovarian regulatory loop concerned with the promotion of the preovulatory cascade. 相似文献
996.
The binding of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) to its intestinal receptor was studied in chicks fed a phosphorus (P)-deficient diet. The equilibrium association constant (Ka) was determined by Scatchard analysis. Association (Kass) and dissociation (Kdis) rate constants were determined in experiments on hormone uptake and release respectively. The Ka, determined at 4, 12 and 19 degrees C, decreased progressively during P deficiency, due to the decrease in Kass, but Kdis was not affected. During prolonged P deficiency the concentration of binding sites (Nmax) also decreased. Duodenal calcium-binding protein (CaBP) increased during 10 days of P deficiency and then decreased. The long-term decrease in receptor affinity and Nmax may account for the observed reduction in receptor occupancy and the decrease in the high level of intestinal CaBP stimulated during early P deficiency. The resulting decrease in Ca absorption may minimize the hypercalcaemia induced by the deficiency. 相似文献
997.
A Hurwitz C Brautbar A Milwidsky P Vecsei A Milewicz D Navot A R?sler 《The Journal of clinical endocrinology and metabolism》1985,60(4):631-638
Studies in three families (A, B, and C) revealed five patients with congenital adrenal hyperplasia (CAH) due to partial and combined 21- and 11 beta-hydroxylase deficiency. One patient (A-11 1), a 23-yr-old severely virilized chromosomal female, was reared as a male, and two females (B-11 2 and C-1) complained only of hirsutism, acne, and menstrual abnormalities. Patients A-11 2 and B-11 8 (17 1/2 and 10 yr old) were asymptomatic and detected by finding an HLA genotype identical to that of their respectively affected brother and sister. Three patients (A-11 1, A-11 2, and C-1) had moderate hypertension. In spite of the wide range of clinical manifestations, all individuals had elevated androgen levels, while cortisol secretion was severely impaired only in A-11 2. 21-Hydroxylase deficiency was diagnosed on the basis of markedly increased plasma and urinary levels of 17-hydroxyprogesterone (17-OHP) and 21-deoxycortisol and their respective urinary metabolites pregnanetriol and pregnanetriolone. PRA was elevated in three patients, while urinary aldosterone was normal or increased. 11 beta-Hydroxylase deficiency was diagnosed on the basis of increased 11-deoxycortisol and deoxycorticosterone in plasma and tetrahydro-11-deoxycortisol and deoxycorticosterone in urine, particularly after ACTH administration. In contrast to classical 11 beta-hydroxylase deficiency CAH, urinary 18-hydroxycorticosterone and 18-hydroxy-11-deoxycorticosterone were normal or elevated. The nature and mechanism of a combined enzymatic defect are unknown. The coincidental presence in a single individual of the mutant genes for both 21- and 11 beta-hydroxylase deficiency CAH is very unlikely to occur. Two alternative hypotheses may explain our findings. One is the existence of a genetically inherited abnormal (or aberrant) 11 beta-hydroxylase, whose affinity for its normal substrate is changed for an abnormal one (17-OHP). As a result, 11 beta-hydroxylation of 11-deoxycortisol is deficient while 17-OHP 11 beta-hydroxylation is markedly enhanced. Thus, both 11-deoxycortisol and 21-deoxycortisol as well as their urinary metabolites accumulate. The ability for 18-hydroxylation, however, remains normal. In this case, 21-hydroxylase is not deficient, yet 21-deoxycortisol cannot be further hydroxylated to cortisol, since this steroid is not a suitable substrate for the enzyme. Such a disorder may represent a new allelic variant of 11 beta-hydroxylase deficiency CAH, which, similar to 21-hydroxylase deficiency, is completely linked to the HLA complex.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
998.
BACKGROUND & AIMS: The molecular mechanisms underlying pancreatitis are largely unknown. The goal of this study was to identify an early genetic event that correlated with pancreatitis. METHODS: Differential display of messenger RNAs (mRNAs) was conducted on normal pancreas vs. those of animals with secretagogue-induced pancreatitis. Northern blots from normal animals and animals with experimental acute pancreatitis were probed with cloned complementary DNAs for chemokines. Pancreatitis was induced with cerulein and by retrograde injection of bile salts. Immunocytochemistry was used to identify the source of chemokine expression. Pyrrolidine dithiocarbamate was tested for effects on chemokine expression and pancreatitis. RESULTS: A differentially amplified band was consistently observed early after cerulein hyperstimulation. This band was identified as a portion of the mob-1 gene, an alpha-chemokine. Northern analysis indicated that mRNAs for mob-1 and another chemokine, mcp-1, were induced after cerulein hyperstimulation in vivo. mob-1 mRNA was also induced by retrograde injection of bile salts and by cerulein in acinar cells in vitro. mob-1 protein was localized to exocrine cells in pancreata of diseased animals. Pyrrolidine dithiocarbamate inhibited both chemokine gene expression and early inflammatory characteristics of pancreatitis. CONCLUSIONS: Chemokines are induced in acinar cells by treatments that induce pancreatitis and may play an important role in the early stages of the disease. (Gastroenterology 1997 Dec;113(6):1966-75) 相似文献
999.
Arthur E. Weyman Harvey Feigenbaum Roger A. Hurwitz Donald A. Girod James C. Dillon Sonia Chang 《The American journal of cardiology》1976,37(3):358-365
Ten patients with discrete subvalvular aortic stenosis were examined using a real time, high resolution cross-sectional echocardiographic scanner. There were two patients (Group I) with a thin discrete subvalvular membrane, five (Group II) with a more extensive area of subvalvular narrowing and three with a residual area of outflow tract obstruction after surgical revision (Group III). In patients with a thin obstructing membrane (Group I), two distinct linear echoes were observed in the outflow tract. These echoes were not continuous with the walls of the outflow tract and showed some dynamic motion during the cardiac cycle. In four of the five patients with diffuse outflow tract narrowing (Group II), a relatively extensive area of inward bowing of both the anterior and posterior margins of the outflow tract was noted. In the fifth case, there was a prominent localized shelf-like increase in thickness of the basal portion of the muscular septum with a corresponding echo projecting anteriorly from the mid-portion of the anterior mitral leaflet. The three cases examined after surgical revision of the outflow tract (Group III), had different patterns of outflow tract narrowing, but narrowing was clearly demonstrated. This study suggests that cross-sectional echocardiography offers an alternative and probably improved method for the noninvasive visualization of the left ventricular outflow tract. 相似文献
1000.
Irish setter dogs affected with rod/cone dysplasia contain a nonsense mutation in the rod cGMP phosphodiesterase beta-subunit gene. 总被引:8,自引:3,他引:8
下载免费PDF全文
![点击此处可从《Proceedings of the National Academy of Sciences of the United States of America》网站下载免费的PDF全文](/ch/ext_images/free.gif)
M L Suber S J Pittler N Qin G C Wright V Holcombe R H Lee C M Craft R N Lolley W Baehr R L Hurwitz 《Proceedings of the National Academy of Sciences of the United States of America》1993,90(9):3968-3972
Irish setter dogs affected with a rod/cone dysplasia (locus designation, rcd1) display markedly elevated levels of retinal cGMP during postnatal development. The photoreceptor degeneration commences approximately 25 days after birth and culminates at about 1 year when the population of rods and cones is depleted. A histone-sensitive retinal cGMP phosphodiesterase (PDE; EC 3.1.4.35) activity, a marker for photoreceptor PDEs, was shown previously to be present in retinal homogenates of immature, affected Irish setters. Here we report that, as judged by HPLC separation, this activity originates exclusively from cone photoreceptors, whereas rod PDE activity is absent. An immunoreactive product the size of the PDE alpha subunit, but none the size of the beta subunit, can be detected on immunoblots of retinal extracts of affected dogs, suggesting a null mutation in the PDE beta-subunit gene. Using PCR amplification of Irish setter retinal cDNA, we determined the complete coding sequence of the PDE beta subunit in heterozygous and affected animals. The affected PDE beta-subunit mRNA contained a nonsense amber mutation at codon 807 (a G-->A transition converting TGG to TAG), which was confirmed to be present in putative exon 21 of the affected beta-subunit gene. The premature stop codon truncates the beta subunit by 49 residues, thus removing the C-terminal domain that is required for posttranslational processing and membrane association. These results suggest that the rcd1 gene encodes the rod photoreceptor PDE beta subunit and that a nonsense mutation in this gene is responsible for the production of a nonfunctional rod PDE and the photoreceptor degeneration in the rcd1/rcd1 Irish setter dogs. 相似文献